BIOE 301 Lecture Sixteen Review of Last Time How do we treat coronary artery disease? CABG PTCA Stent Prevention Progression of Heart Disease
High Blood Pressure High Cholesterol Levels Atherosclerosis Ischemia Heart Failure Heart Attack What is Heart Failure? Heart Failure Heart failure:
Occurs when left or right ventricle loses the ability to keep up with amount of blood flow Can involve the heart's left side, right side or both sides Usually affects the left side first About 5 million Americans are living with heart failure 550,000 new cases diagnosed each year
Quantifying Heart Performance Ejection Fraction (EF) Normal echocardiogram Fraction of blood pumped out of ventricle relative to total volume (at end diastole)
EF = SV/EDV Normal value > 60% Measured using echocardiography http://www.ardingerphoto.com/pcawebsite/card iology/movies/sssmovies/normallao2cycle.html Dilated cardiomyopathy http://www.ardingerphoto.com/pcawebsite/ cardiology/movies/sssmovies/ Left Sided Heart Failure Involves left ventricle Systolic failure
Diastolic failure Ventricle loses ability to relax; muscle has become stiff Can't properly fill during resting period between beats Pulmonary edema Left ventricle loses ability to contract
Can't push enough blood into circulation Blood coming into left chamber from lungs "backs up," causing fluid to leak into the lungs As ability to pump decreases, blood flow slows, causing fluid to build up in tissues throughout body (edema) Congestive Heart Failure Symptoms of Heart Failure Symptom Why It Happens People May Experience: Shortness of breath (also called dyspnea)
Blood "backs up" in pulmonary veins (the vessels that return blood from the lungs to the heart) because the heart can't keep up with the supply. Causes fluid to leak into lungs Breathlessness during activity, at rest, or while sleeping, which may come on suddenly and wake them up. Often have difficulty breathing while lying flat; may need to prop up upper body and head on pillows
Persistent coughing or wheezing Fluid builds up in lungs Coughing that produces white or pink blood-tinged phlegm. Buildup of excess fluid in body tissues (edema) As flow out of heart slows, blood returning to heart through veins
backs up, causing fluid build up in tissues. Swelling in feet, ankles, legs or abdomen or weight gain. May find that shoes feel tight Symptoms of Heart Failure Symptom Why It Happens People May Experience: Increased heart rate To "make up for" loss in pumping capacity,
heart beats faster Heart palpitations, which feel like the heart is racing or throbbing. Confusion, impaired thinking Changing levels of Memory loss and feelings blood substances, such of disorientation. as sodium, can cause confusion Lack of appetite, nausea
Digestive system receives less blood, causing problems with digestion Feeling of being full or sick to their stomach. Tiredness, fatigue Heart can't pump enough blood to meet needs of tissues. Body diverts blood away from less vital organs Tired feeling all the time and difficulty with everyday activities, such as
shopping, climbing stairs, carrying groceries or How Do We Treat Heart Failure? How Do We Treat Heart Failure? Heart Transplant Cardiac Assist Devices Artificial Heart http://www.cbsnews.com/htdocs/health/ heart/framesource.html How Do We Treat Heart Failure? Heart Transplant Heart Transplant
1960s: 1980s: Anti-rejection meds became available (Cyclosporine) Today:
First heart transplants performed About 80% of heart transplant recipients are alive two years after the operation 50% percent survive 5 years Need: 4,000 patients are on the national patient waiting list for a heart transplant Only about 2,300 donor hearts become available for transplantation each year Surgical Procedure http://www.pbs.org/wgbh/
nova/eheart/ transplantwave.html Rejection Risk of rejection is highest right after surgery In one study, first year after transplant: 37% of patients had no rejection episodes 40% had one episode 23% had more than one episode Induction therapy:
Use of drugs to heavily suppress immune system right after transplant surgery Patients keep taking some antirejection drugs for the rest of their life Remember from our vaccine unit: How Do T Cells Identify Virus Infected Cells? Antigen Presentation All cells have MHC molecules on surface When virus invades cell, fragments of viral
protein are loaded onto MHC proteins T Cells inspect MHC proteins and use this as a signal to identify infected cells MHC Receptors Two types of MHC molecules Self-Tolerance
Class I MHC molecules are found on all nucleated cells Class II MHC molecules are found on antigen presenting immune cells T cells which recognize class I MHC-self antigens are destroyed early in development When this fails: auto-immune disease Type 1 diabetes http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/medialib/Image_Bank/CH22/ http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/medialib/Image_Bank/CH22/ Donor MHC Matching
The greater the difference in peptide sequences of MHC receptors between donor and recipient: The stronger the immune response The greater the chance of organ rejection Matching: 200 different histocompatibility antigens Each person has a certain "set
Odds that 2 unrelated people will have the same set are about 1 in 30,000 Transplant coordinators try to match histocompatibility antigens of the donor and the recipient as well as possible to minimize rejection Immunosuppressive Rx Cyclosporine, azathioprine and low-dose steroids Reduce T-cell activation: Immuno-compromised state
T-helper cell CTL activity Caused by alloreactive T-cells within the donor tissue that can cause tissue damage in the recipient Routine heart biopsies to monitor for rejection How To Become An Organ Donor Three steps: 1. Speak with your family about your decision to donate. Make sure they know about your wish to be an organ donor
2. Sign a Uniform Donor Card, and have two family members sign the card as witnesses 3. Carry the card in your wallet at all times. Uniform Donor Card Department of Public Safety (where you obtain drivers licenses) Register Online
https://www.donatelifetexas.org/TXDear_Secure/ default.aspx Why Inform Your Family If you haven't told your family you're an organ and tissue donor -- you're not! Sharing your decision with your family is more important than signing a donor card. In the event of your death, health professionals will ask your family members for their consent to donate your organs and tissues. This is a very difficult time for any family, and knowing your wishes will help make this decision easier for them. They will be much more likely to follow your wishes if you have discussed the issue with them. Remember - signing an organ donor card is NOT enough. Discuss your decision with your family! More About Organ Donation
http://www.organdonor.gov http://www.tdh.state.tx.us/agep/ become.htm http://www.lifegift.org/default.html http://www.lifegift.org/ UD_Organ_Donation.html http://www.shareyourlife.org/ History of Cardiac Devices 1950s and 1960s:
1970s and 1980s: Heart-lung machine Prosthetic materials to close holes between heart chambers Replacement valves
Implantable pacemakers Coronary angiography to diagnose/treat coronary artery disease Intra-aortic balloon pump (IABP) IABP gains wide acceptance as temporary cardiac assist system Cyclosporine, an anti-rejection drug, makes human heart transplants feasible PTCA to treat coronary artery disease with a balloon catheter External & implantable ventricular assist devices enter clinical trials 1990s: External and implantable left ventricular assist devices approved for temporary support as a bridge-to-transplantation Requirements of Mechanical Support
Non-thrombogenic blood contacting surface Pumping action that avoids blood trauma Variable output Small enough to fit in chest cavity Reliable Types of Mechanical Support Temporary: LVADs
Give heart muscle a chance to rest/recover Bridge to transplantation Failure is not catastrophic Permanent: Total Artificial Heart Replace damaged heart muscle Failure is catastrophic How Do We Treat Heart Failure? Left Ventricular Assist
axialpump.jpeg Small Continuous, non-pulsatile flow http://www.texasheartinstitute.org/j2f462s.jpg How Do We Treat Heart Failure? Artificial Heart Artificial Heart - History April 4th, 1969
Haskell Karp became first human to have artificial heart implanted Surgeon Denton Cooley performed operation Artificial Heart - History Denton Cooley Mr. Karp has regained organ function indicated the mechanical heart is feasible Mrs. Shirley Karp
He could not say anything I dont think he was really conscious One day they removed the tube from his throat, they put a sheet over all the apparatuses in back of him and had they medial take their pictures Immediately after this was done they put back the tube and opened up everything that had closed up. Artificial Heart - History
Karp survived 5 days with artificial heart Human heart transplant was performed Karp died 14 hours later Artificial Heart - History Dr. Debakey Dr. Liotta Led team testing artificial heart in animals
Principal scientist developing artificial heart Liottas proposal: Even though 4 of 7 calves died after implant Implant heart in human Debakey rejected proposal Liotta secretly went to Dr. Cooley who agreed IRB was not informed Artificial Heart - History
Dr. Cooley Dr. Debakey seemed to show little interest in ever using it. Dr. Liotta thought he was just wasting his years in a laboratory The time had come to really give it a test and the only real test would be to apply it to a dying patient In those days I didnt feel like we needed
permission I needed the patients consent I think if I had sought permission from the hospital, I think I probably would have been denied and we would have lost a golden opportunity Artificial Heart - History Dr. Debakey I was in Washington when I read in the morning pagers about the use of this artificial heart I was shocked I didnt know he had taken it from the
laboratory Artificial Heart - History No more human trials until the 1980s History of Artificial Heart June 2001 August 2001
http://discover.npr.org/ features/feature.jhtml? wfId=1123833 http://discover.npr.org/ features/feature.jhtml? wfId=1127758 November 2001 http://discover.npr.org/ features/feature.jhtml? wfId=1133260 http://images.usatoday.com/news/_photos/2001-11-30heartguy.jpg History of Artificial Heart
1958: Designed by Drs. Willem Kolff and Tetsuzo Akutsu Polyvinyl chloride device Sustained a dog for 90 minutes http://www.accessexcellence.org/WN/graphics/ jarvik.jpg 1965: Dr. Willem Kolff Silicone rubber heart Tested in a calf http:// www.abiomed.co m/images/
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 http:// www.abiome d.com/ images/ 1982:
Drs. Willem Kolff, Donald Olsen, and Robert Jarvik, Jarvik-7 First to be implanted in a human as destination therapy http://www.ps-lk3.de/images/ABIOCOR.JPG http://static.howstuffworks.com/gif/artificial-heart-abiocordiagram.gif AbioCor Artificial Heart http:// www.heartpioneers .com/
newsimages.html# Cost: $70-100k http://www.cardiocaribe.com/newsite/images/articulos/feb02/ abiocor_hand.jpg Surgical Procedure Surgeons implant energy-transfer coil in the abdomen The chest is opened and patient is placed on a heartlung 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 http://www.heartpioneers.com/images/news/ implant_thumb.jpg http://www.louisville.edu/hsc/medmag/ss01/ images/abio-prep.gif http://www.pbs.org/wgbh/nova/eheart/transplantwave.html
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. 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 >30 days Serious non-cardiac disease Pregnancy Psychiatric illness (including drug or alcohol abuse) Inadequate social support system 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
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