Download March 20, 2017 - Transplant Awareness Organization

Advances in Heart
Transplantation and Mechanical
Circulatory Support
Jeffrey Alexis, MD
University of Rochester Medical Center
1st Heart Transplant
• Dr. Christiaan Barnard
• South Africa, December 3 1967
• Donor was a 25 year old woman who
died following an auto accident
• Recipient was a 55 year old man, lived
18 days, died from pneumonia
• Subsequent Rush to do Heart Transplants
• 1st transplant in US: December 6, 1967
• Dr. Adrian Kantrowitz- Maimonides Medical
Center in Brooklyn NY
• 18 day old male received a transplant from 2
day old male, died 6 hours later- acidosis
• 3rd Heart Transplant: Dr. Christiaan Barnard
January 2, 1968, 58 yr old man received a heart
from a 24 year old man
• 1st Adult US Transplant: January 6, 1968, Dr.
Norman Shumway, Stanford University, 54 year
old man received a heart from a 43 year old
man, recipient died 15 days later of multiple
systemic complications
• 100 heart transplants done in 1968
• Poor outcomes, 80% of patients died within 1
year
• Immunosuppression was the major problem
• 18 transplants done in 1970
Immunosuppressive Drugs in
Organ Transplantation
Year
1959
Therapy
Total Body irradiation
1960-1962
6-Mercaptopurine and azathioprine
1962-1963
Steroids used systemically
1978
Cyclosporine
1989
Tacrolimus
1997
Mycophenolate mofetil
1998
Sirolimus
Immunosuppressive Drugs
Azathioprine
•Derived from 6-mercaptopurine
•Inhibits cell cycle; impairs DNA synthesis
•Developed by Gertrude Elion and George
Hitchings who won a share of the 1988 Nobel
Prize
Immunosuppressive Drugs
Azathioprine
Side Effects
•Myelosuppression
Leukopenia (White blood cell count)
Thrombocytopenia (Platelet count)
Anemia (Red blood cell count)
•Malignancies (cutaneous)
--
Corticosteroids
•Anti-inflammatory- inhibit leukotrienes and
prostaglandins
•Immunosuppressive- Impair rate of
transcription of genes that encode regulatory
cytokines.
Corticosteroids
•Inhibit white blood cell transmigration
through blood vessels
•Reduce adhesion molecule expression
Corticosteroids
Side Effects
•Diabetes
•Obesity
•Cushingoid Features
•Wound Healing
•Bone Disorders
•Colonic perforation
•Hypertension
Cyclosporine
•Inhibits Calcineurin pathway- forms
complex with cellular protein called
immunophilin (Cyclophilin). Inhibits
production of IL-2 and other cytokines.
•Revolutionized solid organ transplantation
Immunosuppressive Drugs
Cyclosporine
•Side effects
•Kidney Disease
•High blood pressure
•Elevated lipids
Tacrolimus
•First isolated in 1984 from bacteria Streptomyces
tsukubaensis
•First used as replacement therapy for cyclosporine in liver
transplant patients with intractable rejection
•Inhibits Calcineurin.
Immunosuppressive Drugs
Tacrolimus
Side Effects
•Kidney Disease
•Neurologic- tremor, headache
•Glucose intolerance
•Elevated Potassium
Mycophenolate
• Cellcept- blocks the pathway proliferation of T and B cells
• Compared with Azathioprine, reduced mortality at 1 yr
(6.2% vs. 11.4%; p=0.031), reduction in requirement of
treatment for rejection (65.7% vs. 73.7%; p=0.031)
Kobashigawa J et al. Transplantation 1998; 507-515
• Compared with Azathioprine at 3 yrs, risk of death or
repeat transplant reduced (11.8% vs. 18.3%; p<0.01)
Eisen HJ et al. J Heart Lung Transplant 2005;24:517-25.
Mycophenolate
Side Effects:
•GI—Nausea, diarrhea
•Leukopenia
Sirolimus
•Inhibitor of TOR (Target of Rapamycin), a
cytoplasmic enzyme that is critical in
connecting signals from T-cell surface to cell
nucleus for stimulation of growth and
proliferation of lymphocytes
•Side Effects:
•Hyperlipidemia
•Thrombocytopenia (low platelets)
Current State of Heart Transplants
• 1 year survival 85-90%
• Median survival 11 years
• Patients have lived 30 years post
transplant
• 4000 done world wide each year
• 2000 done in the US each year
• Long waiting times
Long Waiting Times
• Number of donors is flat
• Decreased deaths from motor
vehicle accidents and homicides
• No living related donors
Awaiting Transplant- UNOS Status
Status 1A
Status 1B
Status 2
UNOS Region 9
Long Waiting Times
Most transplants are Status 1A
Even as Status 1A, wait can be 1 year!
Many patients wait for transplant in the
hospital
Long Waiting Times, limited number of
organs, has led to increase of Mechanical
Circulatory Support:
Ventricular assist devices (VAD)
Total Artificial Heart (TAH)
Extracorporeal Membrane Oxygenation
(ECMO)
History of MCS
• 1966/67-First Ventricular Assist Device
placed by Dr. Michael Debakey- Methodist
Hospital in Houston
• 1969- First TAH placed by Dr. Denton
Cooley, at the Texas Heart Institute - device
lasted 64 hours
• Dr. Cooley used Dr. Debakey’s device
without authorization- 40 yr feud
History of MCS
• 1982- First totally implanted artificial heart
for permanent use, was implanted- Jarvik 7
to patient Barney Clark who survived 112
days
History of MCS
• 1986 First pneumatic pulsatile LVAD – Dr.
Bud Frazier- Heartmate 1000 IP
• 1988- First continuous flow pumpHemopump
HeartMate II LVAD
Heartware LVAD
HeartMate3 LVAD
Ventricular Assist Devices
• No wait time for implant
• Can be placed as bridge to transplant or
as destination therapy
• Median survival 4 years
• Heartware device can be used to
support the left heart and the right heart
Ventricular Assist Devices
• While not common, heart function can
sometimes improve while a patient is
supported with a VAD
• The VAD can sometimes be removed
(this is not common)
ECHO
ECHO
Syncardia TAH
Syncardia TAH
Total Artificial Heart
• Beneficial when patient has left and right
heart disease
• Beneficial when patient has dangerous
arrhythmias- especially ventricular
tachycardia
Extracorporeal
Membrane
Oxygenation
ECMO
Can stabilize patients until stable for longer
term therapy or heart function recovers
Patient Management
• Assess Severity of Illness
• Assess if Sick Enough for Advanced
Heart Failure Therapy
• Assess Candidacy of Advanced HF
Therapy
• Recommend Treatment