professor sir magdi yacoub, frs imperial college london heart science centre

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Professor Sir Magdi Yacoub, FRSImperial College London

Heart Science Centre

CARDIC REPLACEMENT FOR ESHD need,supply,dreams

Madrid2009

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

Chronology

1. Historical perspective -need/supply

2. Definitions “Long term”-Dreams’

3. Results

4. The end of the beginning

5. The future

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

Historical perspectives

1. 60 years ago: fantasy for the future

2. 40 years ago: clinical introduction

a) Enthusiastic reception

b) Moratorium

c) Steady progress-massive neeed.

3. results (longtherm)

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

Definitions

Long term (DREAMS)

Expectations – moving target

- 5 year survival (cancer model)

- 10-15-20 years

- Age matched normal population

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

Results

ISHLT 2007

Transplant “half-life” = 10 years for adult And paediatric recipients

Conditional half-life for those who survive 1 year = 13 years

Constant attrition of survival 3.4% per year

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation Long Term Results

Twenty year survival

Stanford 12.5% 1968-1987

Harefield 25% 1980-1985

Fifteen year survival

Different series 20-33%

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

The end of the beginning

With maturity comes responsibility

Why only less than 12.5-25% survive 20 years

No match to general population

Constant hazard function of death of 3.4% year

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

Causes of attrition in survival and quality of life

1. Graft coronary disease

2. Malignancy 10-100 fold

3. Renal dysfunction

4. Infection

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

Long term outcome after Heart Transplantation

The Future

1. Personalized medicine (Taegtmeyer, Barton, Yacoub, Nature 2006)

2. Improving donor quality and availability (perfusion devices)

3. Early detection and treatment of rejection, cancer, renal dysfunction

4. Newer immunosuppression

5. The Holy Grail - Specific Immune Tolerance

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Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

The Quest for Medawar’s The Quest for Medawar’s ToleranceTolerance

Issues

Who is Medawar?

What is the Quest for Tolerance?

What have we done about it?

What does the future hold?

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

The Quest for Medawar’s The Quest for Medawar’s ToleranceTolerance

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

The Quest for Medawar’s The Quest for Medawar’s ToleranceTolerance

Isn’t he beautiful?

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

The Quest for Medawar’s The Quest for Medawar’s ToleranceTolerance

Peter Medawar - 1915-1987

1) Scientist “A tireless searcher for the truth, merciless debunker of myths”

2) “Father” of organ transplantation

3) A philosopher

4) A “humanist”

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

The Quest for Medawar’s The Quest for Medawar’s ToleranceTolerance

The Threat and the Glory

“It is the great glory as it is the great threat of science that

everything which is in principle possible can be done if the

intention to do it is sufficiently resolute.”

Peter Medawar

arefieldH O S P I T A L

Imperial CollegeOF SCIENCE TECHNOLOGY AND MEDICINE

The Quest for Medawar’s Tolerance

The Future

- Induction of Medawar’s Tolerance is badly

needed to rejuvinate tissue and organ

transplantation

- The question is how resolute is our clinical

and research community?