This is a brief introduction to the topic for undergraduate medical students.

1. Cardiac Transplantation
Dr. Muhammad Usman Shams

2. Indications for Cardiac Transplantation
• Cardiogenic shock requiring mechanical assistance.
• Refractory heart failure with continuous inotropic infusion.
• Progressive symptoms with maximal therapy.
• Severe symptomatic hypertrophic or restrictive
cardiomyopathy.
• Medically refractory angina with unsuitable anatomy for
revascularization.
• Life-threatening ventricular arrhythmias despite aggressive
medical and device interventions.
• Cardiac tumors with low likelihood of metastasis.
• Hypoplastic left heart and complex congenital heart disease.

3. Indications of Cardiac Transplantation
• Patients should receive maximal medical therapy before being
considered for transplantation. They should also be considered for
alternative surgical therapies including CABG, valve repair /
replacement, cardiac septalplasty, etc.
• VO2 (oxygen carrying capacity) has been used as a reproducible
way to evaluate potential transplant candidates and their long term
risk. Generally a peak VO2 >14ml/kg/min has been considered “too
well” for transplant as transplantation has not been shown to
improve survival over conventional medical therapy. Peak VO2 10
to 14 ml/kg/min had some survival benefit, and peak VO2 <10 had
the greatest survival benefit.

4. Contraindications
to Cardiac
Transplantation

5. Evaluation of Cardiac Transplantation
Recipient
• Right and Left Heart Catheterization.
• Cardiopulmonary testing.
• Labs including BMP, CBC, LFT, UA, coags., TSH, UDS,
ETOH level, HIV, Hepatitis panel, PPD, CMV IgG, RPR /
VDRL, PRA (panel of reactive antibodies), ABO and Rh blood
type, lipids.
• CXR, PFT’s including DLCO, EKG.
• Substance abuse history and evidence of abstinence for at
least 6 months and enrollment in formal rehabilitation.
• Mental health evaluation including substance abuse hx and
social support.
• Financial support.
• Weight no more than 140% of ideal body weight.

6. Cardiac Donor
• Brain death is necessary for any cadaveric organ
donation. This is defined as absent cerebral function
and brainstem reflexes with apnea during hypercapnea
in the absence of any central nervous system
depression.
• There should be no hypothermia, hypotension, metabolic
abnormalities, or drug intoxication.
• If brain death is uncertain, confirmation tests using EEG,
cerebral flow imaging, or cerebral angiography are
indicated.

7. Cardiac Donor – Exclusion Criteria
• Age older than 55 years.
• Serologic results (+) for HIV, Hepatitis B or C.
• Systemic Infection.
• Malignant tumors with metastatic potential (except primary brain
tumors)
• Systemic comorbidity (diabetes mellitus, collagen vascular disease)
• Cardiac disease or trauma
• Coronary artery disease
• Allograft ischemic time estimated to be > than 4-5 hours
• LVH or LV dysfunction on echocardiography
• Death of carbon monoxide poisoning
• IV drug abuse.

8. Matching Donor and Recipient
• Because ischemic time during cardiac transplantation is
crucial, donor recipient matching is based primarily not on
HLA typing but on the
– severity of illness
– ABO blood type (match or compatible),
– response to PRA
– donor weight to recipient ratio (must be 75% to 125%)
– geographic location relative to donor
– length of time at current status.

9. Surgical Transplantation Techniques
• Orthotopic implantation is the most common – it involves
complete explantation of the native heart.
• Heterotopic implantation is an alternative technique in
which the donor heart functions in parallel with the
recipient’s heart.

10. Physiologic concerns of Transplant
• Biatrial connection means less atrial contribution to
stroke volume.
• Resting heart rate is faster (95 to 110 bpm) and
acceleration of heart rate is slower during exercise
because of denervation.
• Diurnal changes in blood pressure are abolished.
• Diastolic dysfunction is very common because the
myocardium is stiff from some degree of rejection and
possibly from denervation.

11. Postoperative Complications
• Surgical
– Aortic pseudoaneurysm or rupture at cannulation site
– Hemorrhagic pericardial effusion due to bleeding or
coagulopathy
• Medical
– Severe tricuspid regurgitation
– RV failure
• Pulmonary artery compression
• Pulmonary hypertension
– LV failure
• Ischemia
• Operative Injury
• Acute rejection

12. Postoperative Complications
• Rhythm disturbances
• Asystole
• Complete heart block.
• Sinus node dysfunction with bradyarrhythmias (25% permanent but
most resolve within 1-2 weeks).
• Atrial fibrillation.
• Ventricular tachycardia.
• Coagulopathy induced by cardiopulmonary bypass
• Respiratory failure
• Cardiogenic pulmonary edema.
• Noncardiogenic pulmonary edema.
• Infection.
• Renal or hepatic insufficiency
• Drugs.
• CHF.

13. Postoperative Management
• Initiation of medications, particularly
immunosuppressive agents begins on the day of
the operation.
– Cyclosporin
– Azathioprine
– Solumedrol
– +/- Muromonab-CD3 (OKT3)

14. Postoperative Management
• Pneumocystis carinii prophylaxis is started within the first
week after transplant.
• If patient or donor is CMV positive then ganciclovir is
started on postop day 2.
• Endomyocardial biopsy is performed on postop day 4
and steroids can begin to be tapered if there is no
rejection greater than grade 2b.
• Anticoagulation is started if heterotopic transplantation
has been performed.
• Amylase and lipase are measured on day 3 to detect
pancreatitis.
• ECG’s are obtained every day.

15. Long-term Management
Endomycardial biopsy is performed once a week
for the first month and then less frequently
depending on the presence or absence of
rejection (usual regimen is qweek x 4 weeks,
qmonth x 3 months, q3months in 1st year,
q4months in 2nd year, 1 to 2 times per year
subsequently).

16. Long-term Management
• Cyclosporine levels are checked periodically by
individual center protocols.
• Echocardiography is useful periodically and as an
adjunct to endomyocardial biopsy.
• Cardiac catheterization is performed annually for early
detection of allograft vasculopathy.
• There is probably no need for routine exercise or nuclear
stress testing.

17. Complications - Rejection
• Avoidance with preoperative therapy with cyclosporin,
corticosteroids, and azathioprine.
• If rejection is suspected then workup should include:
measurement of cyclosporine level CKMB level,
echocardiography for LV function, and endomyocardial
biopsy.
• Signs and symptoms of rejection only manifest in the late
stages and usually as CHF (rarely arrhythmias). Due to
close surveillance, most rejection is picked up in
asymptomatic patients.

18. Complications - Rejection
• Hyperacute Rejection: Caused by preformed antibodies
against the donor in the recipient. It occurs within
minutes to hours and is uniformly fatal. PRA screening
is the best method in avoiding hyperacute rejection.
• Acute Cellular Rejection: Most common form and occurs
at least once in about 50% of cardiac transplant
recipients. Half of all episodes occur within the first 2 to
3 months. It is rarely observed beyond 12 months
unless immunosuppression has been decreased.

19. Complications - Rejection
• Vascular (Humoral) Rejection: not well defined.
– Characterized by immunoglobulin and complement in
the microvasculature with little cellular infiltrate.
– It is associated with positive cross match,
sensitization to OKT3, female sex, and younger
recipient age.
– It is more difficult to treat than acute cellular rejection,
is associated with hemodynamic instability, and
carries a worse prognosis.

20. Staging of Acute Rejection
• If acute rejection is found, histologic review of endomyocardial
biopsy is performed to determine the grade of rejection.
• Grade 0 — no evidence of cellular rejection
• Grade 1A — focal perivascular or interstitial infiltrate without
myocyte injury.
• Grade 1B — multifocal or diffuse sparse infiltrate without myocyte
injury.
• Grade 2 — single focus of dense infiltrate with myocyte injury.
• Grade 3A — multifocal dense infiltrates with myocyte injury.
• Grade 3B — diffuse, dense infiltrates with myocyte injury.
• Grade 4 — diffuse and extensive polymorphous infiltrate with
myocyte injury; may have hemorrhage, edema, and microvascular
injury.

21. Complications - Infection
• There are two peak infection periods after
transplantation:
• The first 30 days postoperatively: nosocomial infections
related to indwelling catheters and wound infections.
• Two to six months postoperatively: opportunistic
immunosuppresive-related infections.
• There is considerable overlap, however as fungal
infections and toxoplasmosis can be seen during the first
month.
• It is important to remember that immunosuppressed
transplant patients can develop severe infections in
unusual locations and remain afebrile.

22. Opportunistic Infections
• CMV
• Toxoplasma gondii
• Pneumocystis carinii
• Aspergillus

23. Complications - Malignancy
• Transplant recipients have a 100-fold increase in the prevalence of
malignant tumors as compared with age-matched controls.
• Most common tumor is posttransplantation lymphoproliferative
disorder (PTLD), a type of non-Hodgkin’s lymphoma believed to be
related to EBV.
• The incidence is as high as 50% in EBV-negative recipients of EBV-positive
hearts.
• Treatment involves reduction of immunosuppressive agents, administration
of acyclovir, and chemotherapy for widespread disease.
• Skin cancer is common with azathioprine use.
• Any malignant tumor present before transplantation carries the risk
for growth once immunosuppresion is initiated because of the
negative effects on the function of T-cells.

24. Complications - Hypertension
• As many as 75% of transplant recipients treated with
cyclosporine or corticosteroids eventual develop
hypertension.
• Treatment is empiric with a diuretic added to a calcium
channel blocker, B-blocker, or Ace inhibitor.
• If either diltiazem or verapamil is used, the dosage of
cyclosporin should be reduced.

25. Complications - Dyslipidemia
• As many as 80% of transplant recipients eventually have
lipid abnormalities related to immunosuppression
medications.
• These dyslipidemias have been linked to accelerated
allograft arteriopathy.
• These disorders should be treated aggressively with
statins and fibrates to hopefully alleviate transplant
coronary vasculopathy.

26. Outcomes
• The survival rate according to the United States Scientific
Registry for Organ Transplantation reports the 1-year survival
rate to be 82% and 3 year survival rate to be 74%.
• The most common cause of mortality was cardiac allograft
vasculopathy.
• The UNOS data suggested some group differences with 3-
year survival rate for white persons 75%, Hispanics 71%, and
African Americans 68%
• Similar survival rates between men and women.

27. Outcomes
• Poor outcomes are associated with the following
risk factors:
• Age less than 1 year or approaching age 65.
• Ventilator use at time of transplant.
• Elevated pulmonary vascular resistance.
• Underlying pulmonary disease.
• Diffuse atherosclerotic vascular disease.
• Small body surface area.
• The need for inotropic support pre-transplant.
• Diabetes mellitus.
• Ischemic time longer than 4 hours of transplanted heart.
• Sarcoidosis or amyloidosis as reason for transplant (as they
may occur in the transplanted heart).