Lecture 18: Heart Lecture 18: Heart FailureFailure

BIOE 301BIOE 301

3.22.073.22.07Louise OrganLouise Organ

Four QuestionsFour Questions

What are the major health problems What are the major health problems worldwide?worldwide?

Who pays to solve problems in health Who pays to solve problems in health care?care?

How can technology solve health care How can technology solve health care problems?problems?

How are health care technologies How are health care technologies managed?managed?

Heart Disease OutlineHeart Disease Outline The burden of heart disease The cardiovascular system Heart attacks Atherosclerosis

– Open heart surgery– Angioplasty– Stents

What is heart failure How do we treat heart failure?

– Heart transplant– Left ventricular assist devices– Artificial heart

Review of Last TimeReview of Last Time How do we treat coronary artery How do we treat coronary artery

disease?disease?– Percutaneous transluminal coronary

angioplasty PTCAPTCA

– StentStent– Coronary artery bypass graftCoronary artery bypass graft

CABGCABG

– PreventionPrevention

Prevention vs. TreatmentPrevention vs. Treatment Risk Factors for Heart DiseaseRisk Factors for Heart Disease

– Tobacco useTobacco use– High blood pressure High blood pressure

Over 70% not under controlOver 70% not under control

– High cholesterolHigh cholesterol Over 80% not under control Over 80% not under control

– Inappropriate dietInappropriate diet– ObesityObesity– Low levels of physical activityLow levels of physical activity

Super Size MeSuper Size Me

Progression of Heart Progression of Heart DiseaseDisease

High Blood PressureHigh Cholesterol Levels

Atherosclerosis

Ischemia

Heart Attack

Heart Failure

What is Heart Failure?What is Heart Failure?

http://www.pbs.org/http://www.pbs.org/secondopinion/secondopinion/episodes/heartfailure/episodes/heartfailure/

http://www.pbs.org/http://www.pbs.org/wgbh/nova/heart/ wgbh/nova/heart/

Heart FailureHeart Failure

Heart failure:Heart failure:– Occurs when left or right ventricle loses the Occurs when left or right ventricle loses the

ability to keep up with amount of blood flow ability to keep up with amount of blood flow – Can involve the heart's left side, right Can involve the heart's left side, right

side or both sidesside or both sides– Usually affects the left side firstUsually affects the left side first

About 5 million Americans are living About 5 million Americans are living with heart failurewith heart failure

550,000 new cases diagnosed each year 550,000 new cases diagnosed each year

Quantifying Heart Quantifying Heart PerformancePerformance

Ejection Fraction (EF)Ejection Fraction (EF)– Fraction of blood pumped out of Fraction of blood pumped out of

ventricle relative to total volume (at ventricle relative to total volume (at end diastole)end diastole)

– EF = SV/EDVEF = SV/EDV– Normal value > 60%Normal value > 60%– Measured using echocardiographyMeasured using echocardiography

Left Sided Heart FailureLeft Sided Heart Failure Involves left ventricleInvolves left ventricle Systolic failure Systolic failure

– Left ventricle loses ability to contractLeft ventricle loses ability to contract– Can't push enough blood into circulation Can't push enough blood into circulation

Diastolic failureDiastolic failure– Ventricle loses ability to relax; muscle has become Ventricle loses ability to relax; muscle has become

stiffstiff– Can't properly fill during resting period between beatsCan't properly fill during resting period between beats

Pulmonary edema Pulmonary edema – Blood coming into left chamber from lungs "backs Blood coming into left chamber from lungs "backs

up," causing fluid to leak into the lungsup," causing fluid to leak into the lungs– As ability to pump decreases, blood flow slows, As ability to pump decreases, blood flow slows,

causing fluid to build up in tissues throughout body causing fluid to build up in tissues throughout body (edema) (edema)

Congestive Heart FailureCongestive Heart Failure

Symptoms of Heart FailureSymptoms of Heart FailureSymptomSymptom Why It HappensWhy It Happens People May Experience:People May Experience:

Shortness of Shortness of breath (also breath (also called called dyspnea)dyspnea)

Blood "backs up" in Blood "backs up" in pulmonary veins (the pulmonary veins (the vessels that return vessels that return blood from the lungs to blood from the lungs to the heart) because the the heart) because the heart can't keep up heart can't keep up with the supply. with the supply. Causes fluid to leak Causes fluid to leak into lungsinto lungs

Breathlessness during Breathlessness during activity, at rest, or while activity, at rest, or while sleeping, which may come sleeping, which may come on suddenly and wake on suddenly and wake them up. Often have them up. Often have difficulty breathing while difficulty breathing while lying flat; may need to prop lying flat; may need to prop up upper body and head on up upper body and head on pillowspillows

Persistent Persistent coughing or coughing or wheezingwheezing

Fluid builds up in lungsFluid builds up in lungs Coughing that produces Coughing that produces white or pink blood-tinged white or pink blood-tinged phlegm. phlegm.

Buildup of Buildup of excess fluid excess fluid in body in body tissues tissues (edema)(edema)

As flow out of heart As flow out of heart slows, blood returning slows, blood returning to heart through veins to heart through veins backs up, causing fluid backs up, causing fluid build up in tissues. build up in tissues.

Swelling in feet, ankles, Swelling in feet, ankles, legs or abdomen or weight legs or abdomen or weight gain. May find that shoes gain. May find that shoes feel tightfeel tight

Symptoms of Heart FailureSymptoms of Heart FailureSymptomSymptom Why It HappensWhy It Happens People May Experience:People May Experience:

Increased Increased heart rateheart rate

To "make up for" loss To "make up for" loss in pumping capacity, in pumping capacity, heart beats fasterheart beats faster

Heart palpitations, which Heart palpitations, which feel like the heart is racing feel like the heart is racing or throbbing.or throbbing.

Confusion, Confusion, impaired impaired thinkingthinking

Changing levels of Changing levels of blood substances, such blood substances, such as sodium, can cause as sodium, can cause confusion confusion

Memory loss and feelings Memory loss and feelings of disorientation.of disorientation.

Lack of Lack of appetite, appetite, nauseanausea

Digestive system Digestive system receives less blood, receives less blood, causing problems with causing problems with digestiondigestion

Feeling of being full or sick Feeling of being full or sick to their stomach.to their stomach.

Tiredness, Tiredness, fatiguefatigue

Heart can't pump Heart can't pump enough blood to meet enough blood to meet needs of tissues. Body needs of tissues. Body diverts blood away diverts blood away from less vital organs from less vital organs (limb muscles) and (limb muscles) and sends it to heart & sends it to heart & brain.brain.

Tired feeling all the time Tired feeling all the time and difficulty with everyday and difficulty with everyday activities, such as activities, such as shopping, climbing stairs, shopping, climbing stairs, carrying groceries or carrying groceries or walking. walking.

How Do We Treat Heart How Do We Treat Heart Failure?Failure?

Heart Heart TransplantTransplant

Cardiac Assist Cardiac Assist DevicesDevices

Artificial HeartArtificial Heart

Diet Diet modificationmodification– Weight lossWeight loss– Salt intakeSalt intake

Moderate Moderate exerciseexercise

MedicationMedication

http://www.cbsnews.com/htdocs/hehttp://www.cbsnews.com/htdocs/health/heart/framesource.htmlalth/heart/framesource.html

http://video.google.com/videoplay?docid=-7504680635958708617&q=heart+failure+duration%3Ashort&hl=en

How Do We Treat Heart How Do We Treat Heart Failure?Failure?

Balance a lot of issuesBalance a lot of issues– Prevent disease progress Prevent disease progress – Cause of heart failureCause of heart failure

Can it be reversed?Can it be reversed?

– PrognosisPrognosis– CostCost

SC Heart Hospital’s IT solutionSC Heart Hospital’s IT solution

http://video.google.com/videoplay?docid=-http://video.google.com/videoplay?docid=-6557199641577284256&q=heart+failure&h6557199641577284256&q=heart+failure&hl=enl=en

How Do We Treat How Do We Treat Heart Failure?Heart Failure?

Heart TransplantHeart Transplant

Heart TransplantHeart Transplant 1960s:1960s:

– First heart transplants performedFirst heart transplants performed– Limited successLimited success

1980s:1980s:– Anti-rejection meds became available (Cyclosporine)Anti-rejection meds became available (Cyclosporine)

Today:Today:– About 80% of heart transplants are alive two years About 80% of heart transplants are alive two years

after the operation after the operation – 50% percent survive 5 years 50% percent survive 5 years

Need:Need:– ~2 million Americans have CHF~2 million Americans have CHF– 4,000 patients are on the national patient waiting list 4,000 patients are on the national patient waiting list

for a heart transplantfor a heart transplant– Only about 2,500 donor hearts become available for Only about 2,500 donor hearts become available for

transplantation each yeartransplantation each year

Surgical ProcedureSurgical Procedure

http://www.pbs.org/wgbh/nova/eheart/http://www.pbs.org/wgbh/nova/eheart/transplantwave.htmltransplantwave.html

Yes, it’s a little cheesy!Yes, it’s a little cheesy!

RejectionRejection Risk of rejection is highest right after Risk of rejection is highest right after

surgerysurgery– In one study, first year after transplant:In one study, first year after transplant:

37% of patients had no rejection episodes 37% of patients had no rejection episodes 40% had one episode40% had one episode 23% had more than one episode23% had more than one episode

Induction therapy:Induction therapy:– Use of drugs to heavily suppress immune Use of drugs to heavily suppress immune

system right after transplant surgerysystem right after transplant surgery Patients keep taking some anti-rejection Patients keep taking some anti-rejection

drugs for the rest of their lifedrugs for the rest of their life

Remember from our vaccine Remember from our vaccine unit:unit:

How Do T Cells Identify Virus Infected How Do T Cells Identify Virus Infected Cells? Cells? – Antigen PresentationAntigen Presentation– All cells have MHC molecules on surfaceAll cells have MHC molecules on surface

When virus invades cell, fragments of viral When virus invades cell, fragments of viral protein are loaded onto MHC proteinsprotein are loaded onto MHC proteins

T Cells inspect MHC proteins and use this as a T Cells inspect MHC proteins and use this as a signal to identify infected cellssignal to identify infected cells

http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/medialib/Image_Bank/CH22/FG22_05.jpg

http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/medialib/Image_Bank/CH22/FG22_14.jpg

MHC ReceptorsMHC Receptors

Two types of MHC moleculesTwo types of MHC molecules– Class I MHC molecules are found on all Class I MHC molecules are found on all

nucleated cellsnucleated cells– Class II MHC molecules are found on antigen Class II MHC molecules are found on antigen

presenting immune cellspresenting immune cells Self-ToleranceSelf-Tolerance

– T cells which recognize class I MHC-self T cells which recognize class I MHC-self antigens are destroyed early in developmentantigens are destroyed early in development

When this fails: auto-immune diseaseWhen this fails: auto-immune disease– Type 1 diabetesType 1 diabetes

Donor MHC MatchingDonor MHC Matching The greater the difference in peptide sequences The greater the difference in peptide sequences

of MHC receptors between donor and recipient:of MHC receptors between donor and recipient:– The stronger the immune responseThe stronger the immune response– The greater the chance of organ rejectionThe greater the chance of organ rejection

Matching:Matching:– 200 different histocompatibility antigens200 different histocompatibility antigens– Each person has a certain “set”Each person has a certain “set”– Odds that 2 unrelated people will have the same set Odds that 2 unrelated people will have the same set

are about 1 in 30,000are about 1 in 30,000– Transplant coordinators try to match Transplant coordinators try to match

histocompatibility antigens of the donor and the histocompatibility antigens of the donor and the recipient as well as possible to minimize rejectionrecipient as well as possible to minimize rejection

Immunosuppressive RxImmunosuppressive Rx Cyclosporine, azathioprine and low-dose steroids Cyclosporine, azathioprine and low-dose steroids

– Reduce T-cell activation:Reduce T-cell activation: T-helper cellT-helper cell CTL activityCTL activity

Immuno-compromised state Immuno-compromised state – Recipient susceptible to virus-related diseases:Recipient susceptible to virus-related diseases:

B-cell lymphomas (Epstein-Barr virus)B-cell lymphomas (Epstein-Barr virus) Squamous cell carcinomas (human papilloma virus) Squamous cell carcinomas (human papilloma virus) Kaposi's sarcoma (a herpes virus)Kaposi's sarcoma (a herpes virus) Viral infections (cytomegalovirus)Viral infections (cytomegalovirus)

Graft-versus-host diseaseGraft-versus-host disease– Caused by alloreactive T-cells within the donor tissue Caused by alloreactive T-cells within the donor tissue

that can cause tissue damage in the recipient that can cause tissue damage in the recipient Routine heart biopsies to monitor for rejectionRoutine heart biopsies to monitor for rejection

How To Become An Organ How To Become An Organ DonorDonor

Three steps: Three steps: 1.1. Speak with your family about your Speak with your family about your

decision to donate. Make sure they decision to donate. Make sure they know about your wish to be an organ know about your wish to be an organ donor.donor.

2.2. Sign a Uniform Donor Card, and have Sign a Uniform Donor Card, and have two family members sign the card as two family members sign the card as witnesses.witnesses.

3.3. Carry the card in your wallet at all Carry the card in your wallet at all times.times.

Uniform Donor CardUniform Donor Card Department of Public Safety (where you Department of Public Safety (where you

obtain drivers licenses) obtain drivers licenses) Download a Uniform Organ Donor Card Download a Uniform Organ Donor Card In Texas, DEARIn Texas, DEAR

– Donor Education, Awareness, and RegistryDonor Education, Awareness, and Registry– You can register on line, but you still need the You can register on line, but you still need the

card!card!

http://http://www.dshs.state.tx.us/dear/default.shtmwww.dshs.state.tx.us/dear/default.shtm

Why Inform Your Family?Why Inform Your Family?If you haven't told your family you're an If you haven't told your family you're an organ and tissue donor -- you're not!organ and tissue donor -- you're not! Sharing your decision with your familySharing your decision with your family is more is more important than signing a donor card. In the event of important than signing a donor card. In the event of your death, health professionals will ask your family your death, health professionals will ask your family members for their consent to donate your organs and members for their consent to donate your organs and tissues. This is a very difficult time for any family, tissues. This is a very difficult time for any family, and knowing your wishes will help make this decision and knowing your wishes will help make this decision easier for them. They will be much more likely to easier for them. They will be much more likely to follow your wishes if you have discussed the issue follow your wishes if you have discussed the issue with them.with them.

Remember - signing an organ donor card Remember - signing an organ donor card is NOT enough. Discuss your decision is NOT enough. Discuss your decision with your family!with your family!

More About Organ DonationMore About Organ Donation

https://www.texasdear.orghttps://www.texasdear.org– Texas state organ donor registryTexas state organ donor registry

http://www.organdonor.gov/http://www.organdonor.gov/– Goverment site about organ donationGoverment site about organ donation

http://www.shareyourlife.org/http://www.shareyourlife.org/ http://www.unos.org/http://www.unos.org/

– Organization that coordinates Organization that coordinates transplantstransplants

How Do We Treat How Do We Treat Heart Failure?Heart Failure?

Cardiac DevicesCardiac Devices

History of Cardiac DevicesHistory of Cardiac Devices 1950s and 1960s:1950s and 1960s:

– Heart-lung machineHeart-lung machine– Prosthetic materials to close holes between heart chambersProsthetic materials to close holes between heart chambers– Replacement valvesReplacement valves– Implantable pacemakersImplantable pacemakers– Coronary angiography to diagnose/treat coronary artery Coronary angiography to diagnose/treat coronary artery

diseasedisease– Intra-aortic balloon pump (IABP) Intra-aortic balloon pump (IABP)

1970s and 1980s:1970s and 1980s:– IABP gains wide acceptance as temporary cardiac assist IABP gains wide acceptance as temporary cardiac assist

systemsystem– Cyclosporine, an anti-rejection drug, makes human heart Cyclosporine, an anti-rejection drug, makes human heart

transplants feasibletransplants feasible– PTCA to treat coronary artery disease with a balloon catheterPTCA to treat coronary artery disease with a balloon catheter– External & implantable ventricular assist devices enter External & implantable ventricular assist devices enter

clinical trialsclinical trials 1990s:1990s:

– External and implantable left ventricular assist devices External and implantable left ventricular assist devices approved for temporary support as a bridge-to-approved for temporary support as a bridge-to-transplantationtransplantation

Design Requirements of Design Requirements of DevicesDevices

Non-thrombogenic blood contacting Non-thrombogenic blood contacting surfacesurface

Pumping action that avoids blood Pumping action that avoids blood and tissue traumaand tissue trauma

Variable outputVariable output Small enough to fit in chest cavitySmall enough to fit in chest cavity ReliableReliable

Types of Mechanical SupportTypes of Mechanical Support

Temporary: LVADsTemporary: LVADs– Give heart muscle a chance to Give heart muscle a chance to

rest/recoverrest/recover– Bridge to transplantationBridge to transplantation– Failure is not catastrophicFailure is not catastrophic

Permanent: Total Artificial HeartPermanent: Total Artificial Heart– Replace damaged heart muscleReplace damaged heart muscle– Failure is catastrophicFailure is catastrophic

How Do We Treat How Do We Treat Heart Failure?Heart Failure?

LVADsLVADs

LVADLVAD

http://www.j-circ.or.jp/english/sessions/reports/64th-ss/figures/margulies2.jpg

http://www.todayincardiology.com/199811/S8j00931.GIF

http://nypheart.org/img/rematch.jpg

LVADLVAD

http://www.texasheartinstitute.org/ve_pump.jpg

http://www.texasheartinstitute.org/velvad2.jpg

Axial Flow PumpsAxial Flow Pumps Small Continuous, non-pulsatile flow

http://www.pbs.org/wgbh/nova/eheart/images/axialpump.jpeg

http://www.texasheartinstitute.org/j2f462s.jpghttp://www.texasheartinstitute.org/J2Syss.jpg

How Do We Treat How Do We Treat Heart Failure?Heart Failure?

Artificial HeartArtificial Heart

Artificial Heart - HistoryArtificial Heart - History

April 4April 4thth, 1969, 1969– Haskell Karp became first human to Haskell Karp became first human to

have artificial heart implantedhave artificial heart implanted– Surgeon Denton Cooley performed Surgeon Denton Cooley performed

operationoperation Founded the Texas Heart Institute in 1962Founded the Texas Heart Institute in 1962

– Artificial heart had two chambers and Artificial heart had two chambers and blood was pumped by external airbagsblood was pumped by external airbags

– Karp lived for ~2.5 days until a donor Karp lived for ~2.5 days until a donor heart was availableheart was available Although, he died shortly after transplantAlthough, he died shortly after transplant

No more human trials until the 1980sNo more human trials until the 1980s

Artificial Heart – Success?Artificial Heart – Success? Denton CooleyDenton Cooley

– Mr. Karp has regained organ function indicated the Mr. Karp has regained organ function indicated the mechanical heart is feasiblemechanical heart is feasible

Mrs. Shirley KarpMrs. Shirley Karp– He could not say anythingHe could not say anything– I don’t think he was really consciousI don’t think he was really conscious– One day they removed the tube from his throat, One day they removed the tube from his throat,

they put a sheet over all the apparatuses in back they put a sheet over all the apparatuses in back of him and had they media take their picturesof him and had they media take their pictures

– Immediately after this was done they put back the Immediately after this was done they put back the tube and opened up everything that had closed up.tube and opened up everything that had closed up.

Artificial Heart - OutcomeArtificial Heart - Outcome Dr. DebakeyDr. Debakey

– Led team testing artificial heart in animalsLed team testing artificial heart in animals Dr. LiottaDr. Liotta

– Principal scientist developing artificial heartPrincipal scientist developing artificial heart Liotta’s proposal:Liotta’s proposal:

– Even though 4 of 7 calves died after implantEven though 4 of 7 calves died after implant– Implant heart in humanImplant heart in human– Debakey rejected proposalDebakey rejected proposal– Liotta secretly went to Dr. Cooley who agreedLiotta secretly went to Dr. Cooley who agreed– IRB was not informedIRB was not informed

Artificial Heart - HistoryArtificial Heart - History Dr. CooleyDr. Cooley

– Dr. Debakey seemed to show little interest in ever Dr. Debakey seemed to show little interest in ever using itusing it

– Dr. Liotta thought he was just wasting his years in a Dr. Liotta thought he was just wasting his years in a laboratorylaboratory

– The time had come to really give it a test and the The time had come to really give it a test and the only real test would be to apply it to a dying patientonly real test would be to apply it to a dying patient

– In those days I didn’t feel like we needed permissionIn those days I didn’t feel like we needed permission– I needed the patient’s consentI needed the patient’s consent– I think if I had sought permission from the hospital, I I think if I had sought permission from the hospital, I

think I probably would have been denied and we think I probably would have been denied and we would have lost a golden opportunitywould have lost a golden opportunity

Artificial Heart - HistoryArtificial Heart - History

Dr. DebakeyDr. Debakey– I was in Washington when I read in the I was in Washington when I read in the

morning pagers about the use of this morning pagers about the use of this artificial heartartificial heart

– I was shockedI was shocked– I didn’t know he had taken it from the I didn’t know he had taken it from the

laboratorylaboratory This left all three physicians at oddsThis left all three physicians at odds

History of Artificial HeartHistory of Artificial Heart1997:1997:http://www.chron.com/content/http://www.chron.com/content/chronicle/metropolitan/heart/chronicle/metropolitan/heart/heart-history.3-0.htmlheart-history.3-0.html

July 2001:July 2001:Robert Tools (right) receives Robert Tools (right) receives AbioCor’s self-contained artifical AbioCor’s self-contained artifical hearthearthttp://www.cnn.com/2001/http://www.cnn.com/2001/HEALTH/conditions/07/03/HEALTH/conditions/07/03/artificial.heart/artificial.heart/

Nov 2001:Nov 2001:http://www.pbs.org/newshour/http://www.pbs.org/newshour/updates/november01/heart_11-updates/november01/heart_11-30.html30.html

http://images.usatoday.com/news/_photos/2001-11-30-heartguy.jpg

Next Week (Tues 3/27)Next Week (Tues 3/27)

HW 9 is dueHW 9 is due Third Exam is 4/19Third Exam is 4/19 Project presentations are 4/24Project presentations are 4/24 Final Exam is 4/27 or 5/1Final Exam is 4/27 or 5/1