Cardiac Transplantation

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1. Clinical Advances

1960 - Surgical technique reported

1967 - Successful human transplant

1970 - Recipient selection criteria standardized

1973 - Surveillance endocardial biopsy

1977 - Distant donor heart procurement

1980 - Cyclosporine A

Causes of Death
Transplant Volume

2. Etiology or End-Stage Heart Disease

Etiology	Percentage
Ischemia	44.8
Cardiomyopathy	46.2
Valvular	3.5
Congenital	1.8
Rejection	2.1
Other	1.6

3. Recipient Criteria

Terminal heart disease

Reasonable physiological

No renal or hepatic dysfunction

No acute infections

No recurrent pulmonary infections

Psychosocial stability

No alcohol, tobacco or drug abuse

4. Contradictions

Fixed pulmonary vascular resistance

Peripheral vascular disease

Acute malignancy

COPD of chronic bronchitis

Morbid obesity

ABO incompatibility

5. Donor Criteria

Brain death declared

Age <45 (special exceptions)

No re-existent heart disease

Few CAD risk factors

No untreated acute infections

No systemic malignancy

No cardiac trauma

Normal ECG

Normal echocardiogram

Negative HIV and Hepatitis screen

6. Unique Features of Cardiac Recipient

Prone to infection (opportunistic)

Denervated heart physiology

Rejection at any time- few symptoms

7. Immunosuppressive Therapy

Cyclosporine A

Adrenocortical steroids

Azathioprine

OKT3

Anti-thymocyte globulin (ATG)

Immunosuppression

8. Rejection

Endomyocardial biopsy

Acute rejeciton

Hospital

Out-patient

9. Registry Database

Fifteenth Report- 1998

Total Transplants Reported- 45,993

Total Centers Reported- 257

Survival

1 year- 79%

Thereafter- 4% per year mortality

Total Survival
Survival by ERA
Survival by Age
Survival with Retransplant

10. Risk Factors(p value < 0.001)

Previous cardiac transplant

Ventricular support

Mechanical support (VAD)

Recipient < 5 years of age

Recipient > 60 years of age

Donor > 40 years of age

Donor female

Ischemic time >3.5 hours

11. Causes of Death after Transplantation

Rejection

Infection

Technical

CNS

Malignancy

Cause of Death Post Transplant

After First year

Graft Atherosclerosis

Infection

Malignancy- Lymphoma

Rejection

12. Improved Survival

Cyclosporine

Lower chronic steroid dose

Earlier diagnosis of rejection

Better patient selection

Diagnosis of infection

New antimicrobial agents

Medical and surgical experience

13. Functional Status Following Heart Transplant
Post Transplant Functional Status
Post Transplant Work Status
Post Transplant Rehospitalization

EXTENDED OUTLINE

Candidate Selection

-Most often from idiopathic dilated or ischemic cardiomyopathies

-End stagefailure to respond to maximal therapy; need to identify those who are likely to have sudden death or progressing heart failure

-Adequacy of therapy prior to evaluation is key

-Some guidelines for selection of candidates:

EF < 20%

Peak O2 consumption (VO2) < 10cc/kg/min

Cardiac Donor

-Only 10-20% of brain dead patients with suitable hearts become donors; cardiac transplantation is currently limited by donor availability

-Initial screening done by a local organ procurement agency

-Hep C generally OK

-Level of inotropic support

-Cardiovascular risk factors

-Substance abuse

-Ideally, donor body weight 80-120% of recipients weight

-Age limits

-Intensive fluid management of the donor is important; often these people are hypovolemic from trauma or dibetes insipidus

Donor Cardiectomy

-Visualize/palpate the heart

-Divide the:

SVC

Left superior pulmonary vein

Incise IVC

-Clamp aorta

-Administer cardioplegia

-Avoid coronary sinus injury during liver procurement

-Divide aorta and pulmonary artery

Recipient Operation

-Open RA along the AV groove anteriorly

-Extend this incision to CS inferiorly and to the right atrial appendage posteriorly

-Aorta and main pulmonary artery are divide at the valve commissures

-Incise roof of the left atrium between the aorta and SVC

-Connect the atrial incisions and extend the incision to the left atrial appendage

-Incision is then extended along the AV groove posteriorly to the CS

-Check donor heart for PFO

-Donor pulmonary veins are connected to fashion a left atrial cuff

-Left atrial anastomosis is completed and a vent is placed

-Right atrial anastomosis is completed

-Great vessels are anastomosed; PA first

-Deair, pacing wires, choronotropic/inotropic support

Herotopic Cardiac Transplantation

Posttransplant Concerns

-Immunosuppression

as detailed previously

use of tacrolimus as both maintenance therapy and rescue therapy;

Pittsburgh group has evidence to prove that there are fewer repeat episodes of rejection and it is an effective agent for refractory rejection

-Transvenous myocardial biopsy

IJ approach

3-5 specimens

weekly for the first 4 weeks

grading system developed by Billingham

-Coronary graft vasculopathy

-Infection

bacterial are most common followed by viruses, fungi, and protozoans

viral most common between months 1-6

fungal most common between months 1-2

protozoal infections peaked months 3-6

in the first 6 weeks of transplant, CMV, Herpes, or bacterial are equally likely; >2yrs is usually bacterial pneumonia is the most common infection

CMV can be cultured from almost all recipients; consider active infection in anyone with fever, fatigue, lymphocytosis, elevated LFTs , 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

HSV usually causes mucocutaneous infections

Ebstein-Barr infection seems to be related to the development of posttransplant proliferative disorder; most effective treatment appears to be reduction of immunosuppression

Candidiasis is the most common severe fungal infection seen posttransplant; aspergillosis also has a significant cause of death

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

Renal Failure

Most important side effect of cyclosporinfrom 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 failurelate nephrotoxicity is characterized by a slow rise in serum creatinine

Other

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

Survival

One year: >80%

3-5 years: 70%

12 years: ~40%

bridge to transplant > 90% survival

risk factors: previous transplant, preoperative ventillator dependence, age <5 or >60 recipient) 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%).

Infection is the most significant factor in late deaths, accounting for 40%