Cardiac transplantation Flashcards
What agents can you use for vasodilator challenge for assessing PVR before transplant
Milrinone Nitric oxide Nipride Prostaglandin Oxygen
What is the half-life for survival post OHT
10 years is median survival
J Heart Lung transplant 2010; Oct 29 (10) 1083-1141
what are 2001 CCS indications for cardiac transplant
Adavanced function class NHYA III-IV
Poor 1year survival (peak Vo2 < 15 mm/kg/min
Failure to respond to maximal medical therapy
absence of alternative or conventional surgical options
absence of contraindications
potential to undergo rehabilitation post transplant
What are psychosocial issues for transplant
active smoking (3 months stop)
Drug or ETHO (3 months)
Unstable psychiatric conditions
Non-compliance
What body weight contraindications for transplant
Morbid obesity > 140% ideal body weight
Marked Cachexia < 60% of ideal body weight
Osteoporisis-patients with bone mineral density of > 2 SD below normal or at high risk
What are pulmonary pressure indications for not performing transplant
Transpulmonary gradient of > 15
Pulmonary vascular resitanace of > 4
Pulmonary vascular resistance index of > 6
Systolic pulmonary artery pressure > 50 mmhg
What is difference between bi-atrial and b-caval transplant
No difference in mortality
Bicaval—improved exercise tolerance, less need for PPM, less TR, few tachy arrhytmias, slighlty better hemodynamics
complication of bicaval is SVC syndrome
What are risk factors for possible increased mortality in transplant
Older Donors (> 50) Ischemic times; over 4 hours Donor heart dysfunction: regional wall motion abnormalities
Risk factor for mortality with cardiac transplant
A. Previous cardiac transplant
B. Ventricular support/ Mechanical support (VAD) (controversial)
D. Recipient < 5 years of age
E. Recipient > 60 years of age
F. Donor > 40 years of age(controversial)
G. Donor female (some data about gender mismatch outcomes)
H. Ischemic time >3.5 hours (controversial)
What pt will wait the longest for a heart transplant
A type O blood group (can only receive from O)
also a big pt (the size between donor and recipient should be matched at 0.8 to 1.2).
What is the Canadian transplant Status code
Status 4: mechanically assisted (IABP, VAD, ventilation) and in ICU are highest priority
Status 3: High does single or multiple inotropes; pts who have a VAD but are no in ICU
Status 2 Patients requiring hospitalisation
Status 1: pts a home
Why use induction therapy
reduce steroid use and nephrotixicity associated with early and high dose calcineurin inhibitor while minimizing episdoes of rejection
involves short-term use immediately post transplant (day 0 -7) of an intensive anti-T cell regimen.
They are associated with increased risk of infection because the polyclonal antibodies also effect B-cells.
List induction therapy agents
Polyclonal —OKT3; ATG; ATGAM; ALG
OKT3- associated with increased infections and post transplant lymphoproliferative disorder
Monoclonal–Basilizimab and Davlizumab–specially bind the IL-2 reception
Azathioprine (Imuran)
interferes normal purine pathways, inhibiting both DNA and RNA synthesis. Both B and T lymphocyte proliferation is suppressed and secondary antibody synthesis is reduced.
What medication should not be mixed with Azathioprine (Immuran)
Allopurinol
Mycopehnolate Mofetial (Cell Cept)
Purine analogie anitmetabolite that is much more potent and selective then AZA. Both B and T cells are inhibit, leading to a reduction in cell-mediated and humoral immunity.
effective management in acute rejection
has shown increased survival over AZA
Corticosteroids
Primary effect on T lymphocytes
release of cytokines is reduced
IL-2 production is directly and indirectly inhibited
an effect on B-lymphocytes and reducing antibody production
Rapacycin (sirolimus)
ia macrolide antibiotic structurally related to tacrolimus.
Blocking downstream effects of IL-2 and CD28 signaling
Works syndergistic with CyA and MMF
This drug is used only for refractory acute rejection
What are rates of rejection
majority will have at least one rejection in the first year post-transplant
usually detected on routine surveillance
What is the biopsy protocol post transplant
EMBx performed between day 10 to 14
Typically weeks for 4 weeks
After 1st year they do an annual routine until 5 years post-transplant
New rejection classification
Cellular
Grade 0R: none
Grade 1R: 1 focus of interstitial and/or perivascular infiltrate with myocyte damage
Grade 2R: >2 …
Grade 3R: diffuse … With edema, hemorrhage, vasculitis
Humoral
AMR 0: none
AMR 1: presence of histologic feature and immunofluorescence feature ( CD68)
Histologic features are endothelial swelling and immunoglobulins and complement deposition
What is treatment of CMV
Ganciclovir 5mg/kg BID for 14 days followed by 6 mg/kg daily x 5 days per week until day 28
What are best ways to assess for Transplant coronary artery disease
intravascular ultrasound
Coronary angiography
Screening can involve dobutamine stress echo or myocardial perfusion imaging
remember that TCAD is independent of cholesterol levels
Some benefit of Diltiazem in decreased TCAD
What is Post-transplant Lymphoproliferative disorder (PTLD)
refers to all clinical syndromes association with lymphoproliferative post-transplant from mono to malignancies
Ebstein-Bar virus
Primary EBV infection conveys highest risk
More details on PTLD
1) Frequency: Most common tumor in cyclosporine-based immunosuppression
2) Timing: 12-18 months post transplant/also think Peds transplants
3) Location: Intraabdominal most common
4) Etiology: B cell origin induced by Epstein-Barr virus
5) Treatment: Reduce immunosuppression
6) Acyclovir/ Chemotherapy/radiation
What are common skin malignancies
Squamous cell carcinoma Basal Cell Carcinoman Kaposi's sarcoma Cervical Vulvar
What is UNOs classification
Status 1A. Patients that are hospitalized with either IV inotropes, heart assist devices, mechanical ventilation, or have a life expectancy of less than 1 week.
Status 1B. Patients that are not hospitalized but have IV inotropes or a heart assist device.
Status 2. All other active patients, usually seen by a cardiologist every month, with a right-sided heart catheterization performed every 3 months”
Excerpt From: Carlos M. Mery & Joseph W. Turek. “TSRA Review of Cardiothoracic Surgery.” Feedbooks, 2011. iBooks.
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List diagnosis for Heart-Lung transplant
Congenital heart disease Idiopathic pulmonary artery HTN Cystic fibrosis COPD/Fibrosis Acquired heart disease Idiopathic pulmonary fibrosis AAT deficiency emphysema Sarcoidosis Re-transplant
Indication for heart transplant (pathology)
Systolic heart failure
Ischemic
Dilated
Valvular
Systolic heart failure
Ischemic
Dilated
Hypertensive
Not amyloid, HIV, sarcoma
Intractable ischemia or arrhythmia
Hypertrophic CMP
Not responding to other treatment
CHD without Pulmonary hypertension
Cardiac tumour without metastasis
PVR vs TPG
PVR is depend on cardiac output and is calculated by the following equation
MPAP - PCWP /CO
TPG independent of CO
TPG mmHg = PAP mmHg - PCWP mmHg
What is adequate decline when testing reversibility of pulmonary resistance
2.5 Woods or 50% while maintaining an adequate systemic systolic pressure
Hormonal management of cardiac donor
If LVEF < 45
Vasopressin 1u bolus
T3 4mcg bolus
Methylprednisolone 15 mg/kg
Insulin 1u/hr and titrate
Preferential use of dobu or dopa
Monitor with a swan ganz
Preservation solution for cardiac donor
Intracellular ( low sodium, reduce cellular edema)
Wisconsin
Bretschneider
Extracellular ( low potassium, reduce hyperkalemic cell damage and vascular resistance)
St-Thomas
Clesior
Meds with no effect on heart rate in the transplant recipient
Atropine
Digoxin
Complications vs timing of transplant
< 30 d: primary graft dysfunction, MOF, infection
30d to 1yr: infection, PGD, rejection
>1yr: CAV, cancer
NYHA and survival at 1 yr
I : > 95%
II: 80-90%
III: 55-65%
IV: 5-15%
Rates of malignancy post transplant
A. Incidence 1-2 %/year
B. Cutaneous Malignancy
1) Squamous cell carcinoma
2) Basal cell carcinoma
How much does each 1 Wood unit increase the mortality (especially in 1st year)
15%
What agents can be used for assessing pulmonary hypertension reversibility
Nitroprusside Adenosine Prostaglandin E1 Milrinone Inhaled nitric oxide prostacyclin (Aerosolized Iloprost)
Is transplant contraindicated in Amyloid? or DM? in extreme BMI?
Amyloid-controversial. The amyloid deposits will return and 1 year survival reduced
Contraindicated in DM if there is significant end-organ damage
if BMI < 20 or > 35 the results are poor
What effect to Calcium channel blockers have on transplant
Accentuated slowing of SA and AV nodes and may alter cyclosporine levels
What is leading cause of mortality in transplant population? What is most common bacterial agent? What is most common viral? What fungus is most universally fatal? What is rate of P.Carinii?
CMV (greatest risk is in the first 3 months)
Gram-negative (E.Coli and Pseudomonas)
Aspergillus has highest mortality
P.Carinii–occurs in 1 to 10 % and needs a BAL for diasnosis.
Risk factors for developing cardiac allograft vasculopathy
- acute rejection
- Anti-HLA antibodies
- donor age, HTN, Hyperlipidemia, and preexisting DM (all in the donor)
- The side effects of immunosuppresion agent–steroids/calcineurin inhibitor/–
- CMV infection, new on-set diabetes- nephrotoxicity
What is pathophysiology of CAD
subclinical endothelial injury in the coronary artery allograft—immunological processes involving cytokines, inflammatory mediators, complement activation, and leukocyte adhesion molecules—these changes produce inflammation and thrombosis.
may begin several weeks post transplant.
Silent ischemia, ventricular arrhythmias, congestive heart failure, sudden death are presenting features.
What are rates of increased malignancy post transplant
Increased malignancy of 4 to 18%
which is 100 fold greater then general population
lymphoproliferative disorders and carcinoma of the skin are the most common
Risks are higher when monoclonal and polyclonal antibody therapy are added.
What is pathophysiology of lymphoproliferative disorders
Loss of T-Lymphocyte control over Epstein-Barr virus stimulated B-Lymphocyte proliferation is primary mechanism
How often does retransplantation occur and what are indications
Fewer then 3%
early graft failure, allograft coronary artery disease, and refractory acute rejection
What 4 factors are indicated for LVAD based on clinical trials
- Class 4 Heart failure and failed OMT for at least 60 to 90 days
- Left ventricular ejection fraction of < 25%
- Functional limitation with a peak oxygen consumptions of < 12 ml/kg/min or
- Continued need for intravenous inotropic therapy owing to symptomatic hypotension, decreasing renal funtion, or worsening pulmonary congestion
- Appropriate body sise (BSA > 1.5)
1/3 of BTT pts are lose transplant candiancy
17% of DT receive transplant
What is hyper-acute rejection
Most often when a major blood group incompatiability occurs between donor and recipient,
Most common indication for OHT
idiopathic cardiomyopathy
end-stage ischemic heart disease
congenital
valvular heart disease
What is Hyperacute rejection
occurs when major blood group incompatibility exists between donor and recipient.
Acute rejection is unusually earlier than 2 to 4 weeks
What is acute rejection characterized by
inflammatory state of cell infiltrate, with or without damage to cardiac myocyctes
Since 2004 the classification of acute rejection has been changed to what classification
Grade0R–no rejection
Grade 1R-mild rejection
Grade 2R-moderate rejection
Grade 3R-severe rejection
What is mechanism of hyperacute rejection
preexisting IgM alloantibodies
virtually eliminated because of blood checks
Describe Cell-Mediated rejection
Primarily mediated by CD4 T cells
Contraindications to cardiac transplant
Irreversible PVR > 4 woods units Transpulmonary gradient > 15 mmHg Create > 200 (irreversible) Diabetic with end organ damage Recent malignancy (< 5 years) severe PVD Active infection psychosocial issues Marked obestity (> 140% ideal body weight Severe Osteoporsis
