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Cardiac Transplantation

Cardiac Transplantation

1. Clinical Advances

A. 1960 - Surgical technique reported
B. 1967 - Successful human transplant
C. 1970 - Recipient selection criteria standardized
D. 1973 - Surveillance endocardial biopsy
E. 1977 - Distant donor heart procurement
F. 1980 - Cyclosporine A

2. Etiology or End-Stage Heart Disease

EtiologyPercentage
Ischemia44.8
Cardiomyopathy46.2
Valvular3.5
Congenital1.8
Rejection2.1
Other1.6

3. Recipient Criteria

A. Terminal heart disease
B. Reasonable physiological
C. No renal or hepatic dysfunction
D. No acute infections
E. No recurrent pulmonary infections
F. Psychosocial stability
G. No alcohol, tobacco or drug abuse

4. Contradictions

A. Fixed pulmonary vascular resistance
B. Peripheral vascular disease
C. Acute malignancy
D. COPD of chronic bronchitis
E. Morbid obesity
F. ABO incompatibility

5. Donor Criteria

A. Brain death declared
B. Age <45 (special exceptions)
C. No re-existent heart disease
D. Few CAD risk factors
E. No untreated acute infections
F. No systemic malignancy
G. No cardiac trauma
H. Normal ECG
I. Normal echocardiogram
J. Negative HIV and Hepatitis screen

6. Unique Features of Cardiac Recipient

A. Prone to infection (opportunistic)
B. Denervated heart physiology
C. Rejection at any time- few symptoms

7. Immunosuppressive Therapy

A. Cyclosporine A
B. Adrenocortical steroids
C. Azathioprine
D. OKT3
E. Anti-thymocyte globulin (ATG)

8. Rejection

A. Endomyocardial biopsy
B. Acute rejeciton
1) Hospital
2) Out-patient

9. Registry Database

A. Fifteenth Report- 1998
B. Total Transplants Reported- 45,993
C. Total Centers Reported- 257
D. Survival
1) 1 year- 79%
2) Thereafter- 4% per year mortality

10. Risk Factors(p value < 0.001)

A. Previous cardiac transplant
B. Ventricular support
C. Mechanical support (VAD)
D. Recipient < 5 years of age
E. Recipient > 60 years of age
F. Donor > 40 years of age
G. Donor female
H. Ischemic time >3.5 hours

11. Causes of Death after Transplantation

A. Rejection
B. Infection
C. Technical
D. CNS
E. Malignancy
F. After First year
1) Graft Atherosclerosis
2) Infection
3) Malignancy- Lymphoma
4) Rejection

12. Improved Survival

A. Cyclosporine
B. Lower chronic steroid dose
C. Earlier diagnosis of rejection
D. Better patient selection
E. Diagnosis of infection
F. New antimicrobial agents
G. Medical and surgical experience

13. Functional Status Following Heart Transplant

EXTENDED OUTLINE

1. Candidate Selection

A. Most often from idiopathic dilated or ischemic cardiomyopathies
B. “End stage…failure to respond to maximal therapy”; need to identify those who are likely to have sudden death or progressing heart failure
C. Adequacy of therapy prior to evaluation is key
D. Some guidelines for selection of candidates:
1) EF < 20%
2) Peak O2 consumption (VO2) < 10cc/kg/min

2. Cardiac Donor

A. Only 10-20% of brain dead patients with suitable hearts become donors; cardiac transplantation is currently limited by donor availability
B. Initial screening done by a local organ procurement agency
C. Hep C generally OK
D. Level of inotropic support
E. Cardiovascular risk factors
F. Substance abuse
G. Ideally, donor body weight 80-120% of recipient’s weight
H. Age limits
I. Intensive fluid management of the donor is important; often these people are hypovolemic from trauma or dibetes insipidus

3. Donor Cardiectomy

A. Visualize/palpate the heart
B. Divide the:
1) SVC
2) Left superior pulmonary vein
3) Incise IVC
C. Clamp aorta
D. Administer cardioplegia
E. Avoid coronary sinus injury during liver procurement
F. Divide aorta and pulmonary artery

4. Recipient Operation

A. Open RA along the AV groove anteriorly
B. Extend this incision to CS inferiorly and to the right atrial appendage posteriorly
C. Aorta and main pulmonary artery are divide at the valve commissures
D. Incise roof of the left atrium between the aorta and SVC
E. Connect the atrial incisions and extend the incision to the left atrial appendage
F. Incision is then extended along the AV groove posteriorly to the CS
G. Check donor heart for PFO
H. Donor pulmonary veins are connected to fashion a left atrial cuff
I. Left atrial anastomosis is completed and a vent is placed
J. Right atrial anastomosis is completed
K. Great vessels are anastomosed; PA first
L. Deair, pacing wires, choronotropic/inotropic support

Herotopic Cardiac Transplantation

5. Posttransplant Concerns

A. Immunosuppression
1) as detailed previously
2) use of tacrolimus as both maintenance therapy and rescue therapy;
3) Pittsburgh group has evidence to prove that there are fewer repeat episodes of rejection and it is an effective agent for refractory rejection
B. Transvenous myocardial biopsy
1) IJ approach
2) 3-5 specimens
3) weekly for the first 4 weeks
4) grading system developed by Billingham
C. Coronary graft vasculopathy
D. Infection
1) bacterial are most common followed by viruses, fungi, and protozoans
2) viral most common between months 1-6
3) fungal most common between months 1-2
4) protozoal infections peaked months 3-6
5) in the first 6 weeks of transplant, CMV, Herpes, or bacterial are equally likely; >2yrs is usually bacterial pneumonia is the most common infection
6) CMV can be cultured from almost all recipients; consider active infection in anyone with fever, fatigue, lymphocytosis, elevated LFT’s , neutropenia, and thombocytopenia; 25% will develop invasive GI or pulmonary disease; most severe infections seen in those seronegative prior to operation; Gangcyclovir is used to treat, but its use should be prophylactic
7) HSV usually causes mucocutaneous infections
8) Ebstein-Barr infection seems to be related to the development of posttransplant proliferative disorder; most effective treatment appears to be reduction of immunosuppression
9) Candidiasis is the most common severe fungal infection seen posttransplant; aspergillosis also has a significant cause of death
10) PCP usually presents with fever, dry cough and dyspnea and may be slow to respond to therapy; TMP-SMX or pentamidine prophylaxis can usually prevent it; diagnosis is usually confirmed by methenamine silver stains on BAL fluid; rapid reduction in immunosuppression may exacerbate the process in the lung

6. Renal Failure

Most important side effect of cyclosporin—from afferent arteriolar vasoconstriction and direct tubular cell injury; is dose related to some extent and will improve with reduction in the Cyclosporin dose; oliguria occurs in the early form of renal failure—late nephrotoxicity is characterized by a slow rise in serum creatinine

7. Other

Hirsutism, tremor, gingival hyperplasia, gout, elevated cholesterol, hyperglycermia, osteoporosis, and abdominal surgical complications

8. Survival

A. One year: >80%
B. 3-5 years: 70%
C. 12 years: ~40%
D. Bridge to transplant > 90% survival
E. Risk factors: previous transplant, preoperative ventillator dependence, age <5 or >60 recipient)
F. Risk factors: age >40, female sex, ischemic time >3.5 hours (donor) most common causes of early death: cardiac complications (40%); rejection (19%); infection (16%).
G. Infection is the most significant factor in late deaths, accounting for 40%