BME 301

1
BME 301

• Lecture Nineteen

2
Progression of Heart Disease
High Blood Pressure High Cholesterol Levels
Heart Failure
Atherosclerosis
Heart Attack
Ischemia
3
Review of Last Time

• What is heart failure?
• Occurs when left or right ventricle loses the
  ability to keep up with amount of blood flow
• http//www.kumc.edu/kumcpeds/cardiology/movies/sss
  movies/dilcardiomyopsss.html
• How do we treat heart failure?
• Heart transplant
• Rejection, inadequate supply of donor hearts
• LVAD
• Can delay progression of heart failure
• Artificial heart

4
Artificial Heart - History

• First artificial heart implanted in 1969
• No more human trials until the 1980s

5
History of Artificial Heart
http//images.usatoday.com/news/_photos/2001-11-30
-heartguy.jpg

• http//www.cnn.com/2001/HEALTH/conditions/07/03/ar
  tificial.heart/
• June 2001
• http//discover.npr.org/features/feature.jhtml?wfI
  d1123833
• August 2001
• http//discover.npr.org/features/feature.jhtml?wfI
  d1127758
• November 2001
• http//discover.npr.org/features/feature.jhtml?wfI
  d1133260

6
History of Artificial Heart
1958 Designed by Drs. Willem Kolff and Tetsuzo Akutsu Polyvinyl chloride device Sustained a dog for 90 minutes 1965 Dr. Willem Kolff Silicone rubber heart Tested in a calf
http//www.accessexcellence.org/WN/graphics/jarvik
.jpg
http//www.abiomed.com/images/prodtech/kolff65.jpg

7
History of Artificial Heart
1969 Dr. Domingo Liotta First to be implanted in human as bridge to transplant Patient survived for 3 days with artificial heart and 36 hours more with transplanted heart 1982 Drs. Willem Kolff, Donald Olsen, and Robert Jarvik, Jarvik-7 First to be implanted in a human as destination therapy
http//www.abiomed.com/images/prodtech/liotta.jpg
8
http//www.ps-lk3.de/images/ABIOCOR.JPG
http//static.howstuffworks.com/gif/artificial-hea
rt-abiocor-diagram.gif
9
AbioCor Artificial Heart

• http//www.heartpioneers.com/newsimages.html
• Cost 70-100k

http//www.cardiocaribe.com/newsite/images/articul
os/feb02/abiocor_hand.jpg
10
Surgical Procedure

• Surgeons implant energy-transfer coil in the
  abdomen
• The chest is opened and patient is placed on a
  heart-lung machine
• Surgeons remove the right and left ventricles of
  native heart. This part of the surgery takes two
  to three hours
• Atrial cuffs are sewn to native heart's right and
  left atria
• A plastic model is placed in the chest to
  determine the proper placement and fit of the
  heart in the patient
• Grafts are cut to an appropriate length and sewn
  to the aorta and pulmonary artery
• The AbioCor is placed in the chest. Surgeons use
  "quick connects" -- sort of like little snaps --
  to connect heart to the pulmonary artery, aorta
  and left and right atria.
• All of the air in the device is removed
• The patient is taken off the heart-lung machine

11
http//www.heartpioneers.com/images/news/implant_t
humb.jpg
http//www.louisville.edu/hsc/medmag/ss01/images/a
bio-prep.gif
http//www.pbs.org/wgbh/nova/eheart/transplantwave
.html
12
Clinical Trial of AbioCor

• Goals of Initial Clinical Trial
• Determine whether AbioCor can extend life with
  acceptable quality for patients with less than 30
  days to live and no other therapeutic alternative
  
• To learn what we need to know to deliver the next
  generation of AbioCor, to treat a broader patient
  population for longer life and improving quality
  of life.

13
Clinical Trial of AbioCor

• Patient Inclusion Criteria (highlights)
• Bi-ventricular heart failure
• Greater than eighteen years old
• High likelihood of dying within the next thirty
  days
• Unresponsive to maximum existing therapies
• Ineligible for cardiac transplantation
• Successful AbioFit analysis
• Patient Exclusion Criteria (highlights)
• Heart failure with significant potential for
  reversibility
• Life expectancy gt30 days
• Serious non-cardiac disease
• Pregnancy
• Psychiatric illness (including drug or alcohol
  abuse)
• Inadequate social support system

14
Clinical Trial of AbioCor

• Clinical Trial Endpoints
• All-cause mortality through sixty days
• Quality of Life measurements
• Repeat QOL assessments at 30-day intervals until
  death
• Number of patients
• Initial authorization for five (5) implants
• Expands to fifteen (15) patients in increments of
  five (5) if 60-day experience is satisfactory to
  FDA

15
Consent Form

• http//www.abiomed.com/Fabiocor.html

16
Planning a Clinical Trial

• Two arms
• Treatment group
• Control group
• Outcome
• Primary outcome
• Secondary outcomes
• Sample size
• Want to ensure that any differences between
  treatment and control group are real
• Must consider available

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Example Planning a Clinical Trial

• New drug eluting stent
• Treatment group
• Control group
• Primary Outcome
• Secondary Outcomes

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Sample Size Calculation

• There will be some statistical uncertainty
  associated with the measured restenosis rate
• Goal
• Uncertainty ltlt Difference in primary outcome
  between control treatment group
• Choose our sample size so that this is true

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Types of Errors in Clinical Trial

• Type I Error
• We mistakenly conclude that there is a difference
  between the two groups, when in reality there is
  no difference
• Type II Error
• We mistakenly conclude that there is not a
  difference between the two, when in reality there
  is a difference
• Choose our sample size
• Acceptable likelihood of Type I or II error
• Enough to carry out the trial

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Types of Errors in Clinical Trial

• Type I Error
• We mistakenly conclude that there IS a difference
  between the two groups
• p-value probability of making a Type I error
• Usually set p 1 - 5
• Type II Error
• We mistakenly conclude that there IS NOT a
  difference between the two
• Beta probability of making a Type II error
• Power
• 1 beta
• 1 probability of making a Type II error
• Usually set beta 10 - 20

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How do we calculate n?

• Select primary outcome
• Estimate expected rate of primary outcome in
• Treatment group
• Control group
• Set acceptable levels of Type I and II error
• Choose p-value
• Choose beta
• Use sample size calculator
• WA10
• http//www.bme.utexas.edu/faculty/richards-kortum/
  BME301/students/calendardoc.htm

22
Drug Eluting Stent Sample Size

• Treatment group
• Receive stent
• Control group
• Get angioplasty
• Primary Outcome
• 1 year restenosis rate
• Expected Outcomes
• Stent 10
• Angioplasty 45
• Error rates
• p .01
• Beta 0.2

55 patients required
23
Assignments Due Next Time

• HW8, Part Two
• Presentations
• April 8th
• E-mail from Mark Carlson with details
• Exam Two
• April 13th
• Will cover Vaccines Cancer Detection
• Practice Exam is posted
• TA review session -