Title: Compassionate Allowances Outreach Hearing on Cardiovascular Disease and Multiple Organ Transplants
1Compassionate Allowances Outreach Hearing on
Cardiovascular Disease and Multiple Organ
Transplants
- Clive O. Callender, M.D., FACS
- November 9, 2010
2Howard University Hospital Transplantation
ServicesHeart Transplantation
3El Centro de Transplantes de Howard University
Hospital
-
- In 1973, Dr. Callender developed the first
minority oriented transplant center in this
country.
National Minority Organ Tissue Transplant
Education Program Founder (MOTTEP)
4Waiting list candidates 109,100 as of today
424pm
5Objective
- Current Status of Heart Transplantation
6Growth in Number of Transplanted OrgansSource
2005 OPTN/SRTR
- Organs End of Year Percent Change
- 2003 2004
- Total 25,083 26,539 5.8
-
- Kidney 14,856 15,671 5.5
- Deceased donor 8,388 9,025 7.6
- Living donor 6,468 6,646 2.8
- PTA 117 132 12.8
- PAK 343 418 21.9
- Kidney-pancreas 868 879 1.3
- Liver 5,364 5,780 7.8
- Deceased donor 5,043 5,457 8.2
- Living donor 321 323 0.6
- Intestine 52 52 0.0
- Heart 2,026 1,961 -3.2
7No of Transplanted Organs vs Waiting List 2004
- Recovered Transplanted
Waiting List - Total 25,237 26,539 86,378
- Kidney 12,575 15,671 (9,025) 57,910
- PTA 2,021 132 504
- PAK 418 973
- K-P 879 2,410
- Liver 6,405 5,780 (5,457) 17,133
- Intestine 167 52 196
- Heart 2,096 1,961 3,237
- Lung 1,973 1,168 3,852
- Heart-lung 37 171
-
Source
2005 OPTN/SRTR Annual Report,
8Graft Survival
- Follow-up Period 1 Year 10 Years
- Tx 2002-2003 Tx 1993-2003
- Kidney Deceased Donor
- Graft Survival 89.0 40.5
- Patient Survival 94.6 60.7
- Kidney Living Donor
- Graft Survival 95.1 56.4
- Patient Survival 97.9 76.4
- Kidney-Pancreas
- Kidney Graft Survival 91.7 52.5
- Pancreas Graft Survival 85.8 53.6
- Liver Deceased Donor
- Graft Survival 82.2 52.5
- Patient Survival 81.7 67.0
- Intestine Graft Survival 73.8 22.0
- Heart Graft Survival 86.8 51.1
- Lung Graft Survival 81.4 22.1
- Heart-Lung Graft Survival 55.8 24.6
UNOS/SRTR, 2003
9The History Of Heart Transplantation
3rd December 1967
Nearly 40 years and 70,000 transplants
10(No Transcript)
11Orthotopic Implantation
- Positioning of donor heart
- Creation of left atrial anastomosis
12Orthotopic Implantation
- Completion of right atrial anastomosis (standard
technique)
13Orthotopic Implantation
- Aortic anastomosis
- Pulmonary artery anastomosis
14Orthotopic Implantation
- Completed transplant
- Pacing wires on donor portion of right atrium and
ventricle - Pericardium left open
1515
16ISHLT/UNOS Registry DatabaseNumber of
Transplants Performed
Organ Transplants reported through 2001
Heart 61,533
Heart-Lung 2,935
Lung 14,588
ISHLT
2003
J Heart Lung Transplant 2003 22 610-72.
17Current Trends In Transplant Candidacy
- Older patients, gt 65 years of age
- Generally sicker at time of transplant (Emergent
(status 1A) or urgent transplants (status 1B)
more common) - More women (typically older at time of listing)
- More patients on mechanical circulatory devices
2004 OPTN/SRTR annual report.
1818
1919
2020
2121
2222
23Heart Transplantation
- Although NEVER subjected to a randomized control
trial, heart transplantation is the ONLY therapy
for advanced heart failure observationally
associated with an excellent survival - Advances in close follow-up and newer
immunosuppression have led to improvement in 1
year survival close to 90 - The problem is in survival beyond 1 year which is
still limited (70 at 3 to 5 years, 50 at 10
years)
24Immunosuppression Management During Maintenance
Phase
Low Breakthrough rejection Breakthrough rejection
High Infections Malignancies
Therapeutic NephrotoxicityHypertensionDiabetesNeurotoxicity 30 - 4030 - 555 - 1010 - 30
25Common Immunosuppressive Regimen in 2005
- Primary cyclosporine / tacrolimus(utilized in
conjuction with therapeutic drug monitoring) - Adjunctive mycophenolate mofetil
- Supportive prednisone (only 20 to 30 centers
wean prednisone off if possible) - Additive statins (shown to be immunomodulatory
and associated with improved long term survival)
26Trends in Maintenance Immunosuppression Prior to
Discharge for Heart Transplantation, 1995-2004
Source 2005 OPTN/SRTR Annual Report.
27Major Post Transplant Complications
- Rejection
- Infection
- Cardiac allograft vasculopathy (CAV)
- Hypertension
- Nephrotoxicity
- Malignancy
28Rejection
- Invasive surveillance biopsies are the best
established method for following patients - Typically 13-15 biopsies are done in the first
year - Each biopsy requires a minimum of 3 samples from
3 different sites to be meaningful - A new biopsy grading has been developed for
widespread adoption
29(No Transcript)
30Acute Cellular Rejection
2004 proposed grade 2004 proposed grade 1990 ISHLT
0 No rejection No rejection
1 R Mild Combines former 1A, 1B, and 2
2 R Moderate Former 3A
3 R Severe Former 3B and 4
Treatment required
R Revised Stewart S, et al. JHLT 2005 in press
31Incidence of BPR in Randomized Heart Transplant
Immunosuppression Trials
Trial 1st yearpublished 1st year patients with BPR
Tac vs CSA (European) (n 54 n 28) 1998 73.7 vs 81.5 p 0.444 (1yr)
MMF vs Aza (n 289 n 289) 1998 45 vs 52.9 p 0.055 (1yr)
Tac vs CSA (US) (n 39 n 46) 1999 55 vs 44p 0.046 (6 mo)
Neoral vs Sandimune (n 188 n 192) 1999 42.6 vs 41.7 p ns (6 mo)
32Treatment of Rejection
- Rejection without hemodynamic compromise
- Oral prednisone (100 mg daily for 3 days)
- IV steroids
- Decision dependent on grading severity and time
post transplantation - Steroid resistant rejection with or without
hemodynamic compromise - Cytolytic antibodies IVIG plasmapheresis
photopheresis anti-B cell antibodies rapamycin
methotrexate cyclophosphamide total lymphoid
irradiation
33Rejection
- Cellular rejection remains an important issue
despite the incidence having declined over the
past two decades - Antibody mediated rejection is now recognized as
an important entity but has not been previously
standardized therefore not uniformly incorporated
in trials of immunosuppressive therapy or
investigations pertaining to transplantation
34Specific Causes of Death One Year After Cardiac
Transplantation
CRTD 1990-1999, n 7290
Rejection Infection Non-specific graft
failure Neurologic Sudden
0.025
Malignancy
0.020
0.015
Allograft CAD
Deaths / year
0.010
0.005
0.000
7
1
3
4
6
8
9
10
2
5
Time after transplant (years)
Kirklin JK, et al. J Thorac Cardiovasc Surg 2003
125881-90.
35Long Term Challenges
- Renal failure and metabolic adverse effects
- Cardiac allograft vasculopathy
- Malignancy
36Post-Heart Transplant Morbidity For
AdultsCumulative Incidence for Survivors (Apr,94
- Dec00)
Outcome By 1 year By 5 years
Hypertension 72,4 (N 12,496) 95.1 (N 3,465)
Renal function N 12,511 N 3,776
Normal 74.8 69.1
Renal dysfunction 14.9 17.6
Creatinine gt 2.5 mg/dL 9.0 10.4
Chronic dialysis 1.2 2.5
Renal transplant 0.2 0.4
Hyperlipidemia 48.7 (N 13,183) 81.3 (N 3,899)
Diabetes 24.1 (N 12,487) 32.0 (N 3,444)
CAV 8.2 (N 11,260) 33.2 (N 2,376)
ISHLT
3737
38Renal Function in Transplantation
- CRF developed in 16.5
- Of these, 28.9 required maintenance dialysis or
renal transplantation - CRF significantly associated with increased risk
of death - Relative risk 4.55
- 95 CI 4.38 - 4.74
- p lt 0.001
Liver
Intestine
Lung
Cumulative incidence of CRF
Heart
Heart- lung
12
24
36
48
60
72
84
96
108
120
0
Time since transplantation (months)
Ojo AO et al. N Engl J Med 2003 349931-40.
3939
40The Problem Of Cardiac Allograft Vasculopathy
- Cardiac allograft vasculopathy (CAV) is the
leading cause of death in cardiac transplant
recipients at 5 years post-transplant, accounting
for up to 30 of deaths - CAV is characterized by a proliferation of the
allograft vascular intima, resulting in narrowing
of the vascular lumen - Due to the lack of premonitory signs, CAV often
presents as sudden death, silent myocardial
infarction or severe arrhythmia
41(No Transcript)
42Maximal Intimal Thickening Predicts Cardiac
Events
Prognostically relevant - High plaque burden -
Link with cardiac events
Intimal thickening (mm)
Mehra M et al. J Heart Lung Transplant 1995
14S207-11 Kobashigawa JA et al. J Am Coll
Cardiol 2005 451532-7 Tuzcu EM et al. J Am
Coll Cardiol 2005 451538-42.
4343
44Areas of Current Uncertainty and Future Research
Regarding Malignancies in Heart Transplantation
- Relationship between different immunosuppressants
and cancer risk - Relationship between duration and intensity of
immunosuppression and cancer risk - Efficacy of low or minimal immunosuppression
regimens - Frequency of cancer screening
- Components of cancer screening
Hauptman PJ and Mehra MR. J Heart Lung
Transplant. 200524(8)1111-3.
45Effects on Human Tumor Cell Growth
Growth inhibition ()
Hepatic cancer
Colorectal cancer
Myelodysplasia
Casadio F. Transplant Proc 2005 372144.
46Heart Transplantation2005 and Beyond
- Need for improved immunosuppression with less
rejection, cardiac allograft vasculopathy and
side effects - Need for better non-invasive methods to detect
acute and chronic rejection - Need to focus on improved survival and quality of
life - Challenges in performing long-term adequately
powered multi-centered trials