Cardiac Transplant #2 Flashcards
What are the contra-indications for cardiac transplantation
Age (some say > 65 years)
Active infection
Diabetes with end-organ damage
Signficant symptomatic carotid peripheral vascular disease
Active or recent malgnancy. Ideally, patient should have a 5 year disease-free interval
Excessive obessity (BMI
Chronic renal failure
Hepatic impairment with bilirubin leve of > 25 mmol or ALT/AST ratio > 2, not due to congestion
significant chronic lung disease
Irreversible pulmonary hypertenions
PVR > 5 woods units
Transpulmonary gradient < 18mmHg
Systolic pulmonary hypertension > 60 mmHg.
Evidence of drug abust 6 months
Recent peptic ulcer disease
Poor social supports and history of poor medical compliance
Describe the criteria used for matching donor to recipient in cardiac transplantation
Limit the organ ischemia (< 6 hours)
ABO blood group compatibility
Human leucocyte antigen (HLA) compatibilty
Matching patiet’s size
CMV positive donors given to CMV positive reipients
What are the complications of cardiac transplantation and immunosuppression
Early graft failure Rejection Infection Allograft vasculopathy (50% at 5 years) Malignancy--especially lympohmas and malignant tumors of the skin
What is the classification of organ rejection
Hyperacute rejection–complement-mediate response by pre-existing anti-bodies that are circulating in the recipient. They bind to donor ABO blood group antigens
Acute rejection–T lymphocytes respond to differences between the human leucocyte antigens (HLA) of the donor and recipient
Chronic rejection–manifests its as allograft vasculopathy with diffuse intimal hyperplasi in the coronary arteries of a transplanted heart.
WHat are the agents used for immunosuppression following cardiac transplantation
Corticosteriods
Anti-thymocyte globulin (ATG)
azathioprine
What drugs are used for permanent maintenance phase
CyclosporineA or tracrolimus, which are calcineurin inhibitors that inhibit the transcription of interleukin-2 (IL-2) and T- lymphocyte signal transduction
Azathioprine or mycophenolate mofetil (MMF) which are purine synthesis inhibitors
Corticosteriords, which inhibit the production of cytokines (such as IL-1, TNF-alpha and interferons)
OKT3 which is monoclonal antibody that binds to the CD3 receptor on T-lymphocytes
Daclizumab and basiliximab, which are monoclonal antibodies that bund to the IL-2 receptors of T-lymphocytes
Sirolimus (rapamycin), which stops IL-2-induced activation of T-lymphocytes.
List the major side effect of each of the following immunosuppressive drugs
Tacrolimus (FK 506)
OKT3
Mycophenolate mofeti (CellCept)
Prednisone (Cortiocosteroids)
Tacrolimus = Nephrotxicity
OKT3 = Allergic reaction or increased rate of infection
MMF= Pancytopenia or anemia
Predinsone0- = hypertension/diabetes
List 5 absolute medical contra-indications for donation of a heart for transplantation
Severe structural/valvular heart disease
Severe coronary artery disease
prior myocardial infarction
active malignancy (excluding primary brain or skin cancer)
HIV positive
Death from carbon monoxide poisoning with a carboxy-hemoglobin level > 20%
Prolonged cardiac arrest
List in any order the three most common causes of death following cardiac transplantation
Infection
Rejection
Accelerated Coronary disease
45 year old post transplantation with first ednomyocardial biopsy performed at 8 days and showed Grade 1 A rejection. What are the hallmarks of grade 1, and what is treatment.
Grade 3b and what is treatment
Grade 1 is mild rejection with focal infiltrates of lymphocytes with myocyte damage
No treatment is required.
Grade 3 is diffiuse mononuclear cellular infiltrate with myocyte damage
Treatment is pulse intravenous steriords usually for 3 days
Describe the mechanism of action of the following Cyclosporine Azathioprine Steroids Thymocyte Globulin Monoclonal Antibody
Cyclosporine: prevents the development of T-cells by the inhibition of IL-2. It effects gene activation necessary of IL-2 production by inhibiting the function of calcium calcineurin phosphatase which is essential for IL-2 Gene actiatoin.
Azathioprine (Imuran) is an anti-metaolite that effects both DNA and RNA synthesis and therefore reduces or prevents rapid cells devision thus bluting the ability of the host to generate cytotoxic T- Cells.
Steroids: inhibit a variety of intracellular enzymes that depress DNA, RNA, and protein synthesis there, by depressing cell-mediated immunity.
Immunoglobin ATG) Polyclonal antibody that decreases that level of circulating T-cells by attaching to ciculating lymphyocytes and promoting cytolysis
Define the following
Autograft
Allograft
Heteorgraft
Xenograft
Autograft: organ or tissue from same individual is re-implanted
allograft: organ or tissue from another non identical individual of same species is transplanted
heterograft: organ or tissue from another non identical individual of same species is transplanted
xenograft: organ or tissue from individual of another species is transplanted
List 5 histological changes currently used to grade the severity of cardiac rejection as per ISHLT
Lymphocyte infiltration Necrosis Myocyte damage Inflammatory infiltration Polymorphous infiltration Edema Hemorrhage Vasculitis
On which cells are Class I antigens (HLA-A, B, C)
All cells of an organism
On which cells are Class II antigens (DP, DQ, DR) expressed
On Antigen presenting cells such as B lymphocytes Activated T Lymphocytes Marcophages Dendtritic cells Endothelial cells
Describe the prognostic vale of peak oxygen consumption (Vo2) during exercise as criterior for the evaluation of a potential candidate for heart transplantation
Measurement of peak oxygen consumption during exercise provides an index of overall cardiovascular reserve that is useful both to quantitate functional limitation and to estimate limitation.
Value of 10 to 14 ml/KG/min or lower indicates a very poor prognosis and is generally the cufoff for transplantation.
Patients with peak 16 to 18 ml/kg/min have survival rates similar to that of of a transplantation.
59 year old males with low Po2 (50mmHg) . CXR—abnormal, PEEP lowered it?
What is diagnosis? Describe physiology? Why does PEEP make it worse? How would you manage it?
The patient has an ASD or PFO
Post transplant the right ventricle becomes stif and dysfunction. This increases afterload on the right side. Can develop a right to left shunt.
PEEP increases right ventricular afterload and will increase the right to left shunting
Treatment includes decreasing right ventricular afterload with meds such as milrinone. Nitric oxide may be uses. Can consider closing surgically.
What is the most common organ infected at 3 weeks post Cardiac transplant?
What is most common organism.
lung
CMV
Describe PRA test and its importance in the pre operative assessment of potential heart transplant recipients
Prior to transplantation the serum of a potential recipient is expose to panels of cells that express most HLA types.
This makes it possible to determine if a potential recipient has pre formed antiobodies to common HLA antigens. If a candidate is known to react to more that 10% of the panel specific pre-transplant crossmatching between the the donor and the recipient is required.
CMV remains the most important infection affecting heart transplant recipients and may have both direct and indirect effects on the recipient
List 4 direct manifestations of CMV on heart transplant pts
Fever Mononucleosis (leukopenia and thrombocytopenia) Hepatitis GI ulceration Mycocarditis Pneumonia
What type of virus is CMV
Herpes virus
Direct effects: asympotmatic viral shedding, flu-like illness, pneumonititis, encephalitis, infection of retina,GI tract, pancrease
Indirect effects: allograft rejection, bacterial superinfection, immunosupprresion, chronic graft rejection (Accelerated coronary artery disease)
What features of Donor-recipient matching
Size: the donor great than 80% of recipient body weight
Blood type: identical or compatible
HLA-typig: generally not done
What happens with a cross-match
Crossmatch tests recipient sera for anti-HAL antibodies against range of donor lymphocytes
A positive crossmatch = lymphocyte lysis
The probability of hyperacute rejection is high if the crossmatch is positive
What is treatment of a high PRA levels
IVIG Plasmapheresis Cyclophosphamide Total bone marrow irradiation Rituximab-specific CD20 receptors
What are features of Class II human leukocyte antigents (HLA)
DP, DQ, DR
Helper T cells express CD4
HLA-A, HLA-B and HLA-DR are used for typing
2 possible alleles for each
0-6 antigen mismatch
Registries show reduction in risk with any degree of matching
HLA matching unlikely to influence chronic graft rejection
What is Chronic Allograft vasculopathy
Leading cause of death > 1 year after transplantation Equivalent to chronic rejection in renal vanishing bile ducts in hepatic bronchiolitis obliterans
What is pathogenesis of cardiac allograft vasculopathy
concentric intimal thickening and plaques
may be related to endothelial injury at procurement
CMV infection
Donor age
HLA-mismatch, at DR Locus (?)
What is prevalence of angiographically detecable cardiac allograft vasculopathy
1 year 10-20%
5 years 30-50%
What are features of malignancy after transplantation
Incidence if 2-4% of patients per year
Excessive immunosuppression is a risk factor
Most common are cutaneous: squamous and basal cell carcinoma
Lymphmas are of B cell origian and are related to Epstein-Barr virus
Seronegative recipient with EBV seropositive organ is at 50% risk for developing lymphoproliferative disease
What is rate of Osteoporosis
10% incidence of transplant recipients Rapid during first 6 months after transplant Treatment Calcium Vitamin D Alendronate
What are indications for cardiac transplantations
International society of heart and lung transplantation (ISHLT)
Definite indications
a. HIgh-risk heart failure survival score
b. peak myocardial oxygen consumption < 10 ml/kg/min
c. NHYA class IV heart failure, refractory to maximal medical treatment
d. recurrent hospitalisation for heart failure
e. refractory ischemia, a left ventricular ejection fraction of < 20% and coronary artery disease
f. recurrent symptomatic verntricular arrhythmias refractory to medical treatment, implantable cardio-defrillator
Probable indications
a. medium-risk heart failure, refractory to medical treatment
b. NHYA class III heart failure
c. recent hospitalisations for heart failure
d. Peak myocardial oxygen consumptions < 14ml/Kg/min
