Chapter 105

Heart and Lung Transplantation: 

Surgical Considerations 

Osami Honjo and John G. Coles 

105 

CHAPTER 

INTRODUCTION 

Pediatric heart transplantation has become an effective therapeutic 

strategy for pediatric patients with end-stage cardiomyopathies or 

various types of complex congenital heart disease (CHD). Since 

the first pediatric heart transplantation was attempted in 1967, 

almost 8000 children have undergone heart transplantation world - 

wide. 1 Improvements in medical therapeutic strategies, including 

introduction of cyclosporine and refinement of myocardial pro - 

tection and surgical techniques, have greatly contributed to an 

increase in numbers of heart transplantations over the last two 

decades. Currently, approximately 400 pediatric heart transplanta - 

tions are performed every year worldwide. 1 Recent trends show a 

decrease in the number of heart transplantations as a primary 

treatment for complex CHDs, including hypoplastic left-sided 

heart syndrome (HLHS), because of dramatic improvements in 

staged surgical palliation for patients with HLHS and other singleventricle 

physiology. Instead, there is a growing population with 

failed or failing single-ventricle physiology as a consequence of 

staged surgical palliation requiring heart transplantation. In this 

chapter, we review the current indications, medical and surgical 

strategies, and outcomes of pediatric heart transplantation. 

Special considerations, including a ventricular assist device 

(VAD), ABO-incompatible transplantation, and heart transplan - 

tation from donation after cardiocirculatory death (DCD) are also 

discussed. 

HISTORIC NOTE 

The first pediatric heart transplantation was performed for a 

16-day-old neonate with tricuspid atresia (it was in fact a severe 

form of Ebstein’s disease) in 1967. 2 The patient survived for only 

a few hours; however, this breakthrough operation showed 

the world the feasibility of pediatric heart transplantation. Despite 

the enthusiasm, pediatric heart transplantation did not advance 

in the 1970s mainly because of the lack of effective immuno - 

suppression therapy and myocardial protection. Discovery and 

clinical appli cation of cyclosporine dramatically changed the 

immunosup pressive treatment and improved clinical outcomes 

of heart trans plantation. 3 In 1984, Baby Fae, a newborn with 

HLHS, under went a xenograft heart transplantation, 4 followed 

by the first successful neonatal human-to-human heart trans - 

plantation per formed in 1985 at Loma Linda University Medical 

Center. 5 Owing to those pioneering works, the number 

of pediatric heart trans plantations has grown in an exponential 

manner. 

INDICATIONS AND 

CONTRAINDICATIONS 

Indications 

Indications for cardiac transplantation include children who have 

end-stage cardiac disease and are otherwise well, with a life ex - 

pectancy of less than 1 year and/or poor quality of life. The staging 

for heart failure is shown in Table 105–1. Patients for whom 

cardiac transplantation is indicated should have stage C or D heart 

failure. The pediatric population that requires heart transplanta - 

tion falls into two groups: those with cardiomyopathy and those 

with CHD. The scientific statement published by the American 

Heart Association regarding indications for pediatric heart 

transplantation is summarized in Table 105–2. Those with definite 

indications (Class I) are the patients with stage D or at least stage 

C heart failure with significantly reduced exercise tolerance or 

with life-threatening arrhythmias. Class IIA includes stage C heart 

failure with reactive pulmonary hypertension (PH). Also included 

are some patients with CHD that is not amenable to definitive 

repair. 

Cardiomyopathy 

Cardiomyopathies are the most frequent diagnoses that require 

heart transplantation in patients older than 1 year of age. 1 The 

three major types of cardiomyopathies are dilated, hypertrophic, 

and restrictive. Dilated cardiomyopathy (DCM) is the most 

common subgroup that requires heart transplantation. Various 

underlying diseases, including neuromuscular disorders, past 

episode of myocarditis, familial history, and some chemotherapeutic 

agents, may result in DCM. The overall freedom from 

death or transplan tation is approximately 70% at 1 year and 50% 

at 5 years. 6 Cardio myopathy resulting from a previous episode of 

myocarditis may have a spontaneous recovery. 7 

Hypertrophic cardiomyopathy (HCM) is the second most com - 

mon cardiomyopathy, accounting for approximately 25% of all 

patients with cardiomyopathies. Metabolic disorders such as 

Pompe disease, malformation syndrome such as Noonan syn - 

drome, and neuromuscular disorders may lead to HCM. The 

freedom from death or transplantation of this entity is 83% at 

5 years and 76% at 10 years. It is relatively infrequent that patients 

with HCM require transplantation. 8 

Restrictive cardiomyopathy is a rare subgroup, accounting for 

less than 3% of all patients with cardiomyopathies. 9,10 Although 

rare, this entity often requires transplantation, accounting for 

approximately 15% of patients with all cardiomyopathies requiring

1782 PART 5 ■ Anesthetic, Surgical, and Interventional Procedures: Considerations 

TABLE 105-1. Heart Failure Staging in Pediatric Heart Disease 

Stage Interpretation Clinical Examples 

A 

B 

C 

D 

At risk for developing heart failure 

Abnormal cardiac structure and/or function 

No symptoms of heart failure 


Past or present symptoms of heart failure 


Continuous infusion of intravenous inotropes or prostaglandin E 1 

Mechanical ventilatory and/or mechanical circulatory support 

Congenital heart defects 

Family history of cardiomyopathy 

Anthracycline exposure 

Univentricular hearts 

Asymptomatic cardiomyopathy 

Asymptomatic congenital heart disease 

Repaired or unrepaired congenital heart defects 

Cardiomyopathies 

Same as stage C 

TABLE 105-2. Indications for Pediatric Heart Transplantation (AHA Scientific Statement 2007) 

Class I 

Class IIA 

Class IIB 

Class III 

Recommendations 

Stage D heart failure associated with systemic ventricular dysfunction in cardiomyopathies or congenital 

heart disease 

Stage C heart failure with severe exercise and activity limitations (maximal oxygen comsumption 6 Wood unit/m 2 and/or a transpulmonary pressure gradient >15 mmHg if reactive 

to inotropes or pulmonary vasodilators 

Stage C heart failure with reactive pulmonary hypertension and a potential risk of developing fixed, 

irreversible elevation of PVR 

Certain anatomic and physiologic conditions likely worsen the natural history of functional single 

ventricle, which can lead to use of heart transplantation as primary therapy: 

1) severe stenosis or atresia in proximal coronary arteries 

2) moderate to severe stenosis and/or insufficiency of the atrioventricular and/or semilunar valve(s) 

3) severe ventricular dysfunction 

Several anatomic and physiologic conditions likely worsen the natural history of previously repaired or 

palliated congenital heart disease with stage C heart failure: 

1) pulmonary hypertension and a potential risk of developing fixed, irreversible elevation of PVR 

2) severe aortic or systemic atrioventricular valve insufficiency not amenable to surgical correction 

3) severe arterial oxygen desaturation (cyanosis) not amenable to surgical correction 

4) persistent protein-losing enteropathy despite optimal medical-surgical therapy 

Efficacy of heart transplantation is not established in the following conditions: 

1) previous infection with hepatitis B or C or with HIV infection 

2) history of recent use of illicit drugs or tobacco or a recent history of alcohol abuse 

3) history of psychological, behavioral, or cognitive disorders; poor family support structure; or non - 

compliance with previous therapies 

Heart transplantation is not efficacious in the following conditions: 

1) Severe irreversible disease in other organ system in a part of a multisystemic disease process. 

Multiorgan transplantation may be considered 

2) Severe irreversible fixed elevation of PVR 

3) Presence of severe hypoplasia of the central branch pulmonary arteries and veins 

4) Limited supply of pediatric donors, especially infant donors 

Adopted from Canter et al. Circulation. 2007;115:658–676. 59 Class I, condition for which there is evidence and/or general agreement that heart transplantation is 

useful and effective; Class II, conflicting evidence or a divergence of opinion about usefulness/efficacy; Class IIA, weight of evidence/opinion is in favor of usefulness/ 

efficacy; Class IIB, usefulness/efficacy is less well established by evidence/opinion.

CHAPTER 105 ■ Heart and Lung Transplantation: Surgical Considerations 1783 

transplantation. 11 This subgroup is frequently associated with 

secondary PH due to progressive increase in left ventricular enddiastolic 

pressure, which may complicate transplantation. The 

freedom from death or transplantation is 39% at 5 years and 20% 

at 10 years. 12 Less frequently, patients with left ventricular non - 

compaction or cardiac tumor may be indicated for transplan - 

tation. 

Congenital Heart Disease (CHD) 

Indications of heart transplantation for patients with CHD fall 

mainly into two categories: (1) heart transplantation as a primary 

therapy and (2) heart transplantation for previously repaired or 

palliated complex CHD. Diagnoses in heart transplant recipients 

older than 6 months of age with previously repaired or palliated 

CHD are shown in Table 105–3. More than half of the candidates 

have a functional single ventricle. 13 

Primary Heart Transplantation for Unrepaired 

Complex Congenital Heart Disease 

Since Loma Linda University pioneered neonatal or infantile heart 

transplantation for patients with HLHS as a primary surgical 

therapy, HLHS has been a leading CHD in this category, from the 

1980s to the early 1990s. The 5-year survival with neonatal 

transplantation in patients with HLHS was 84%. 14 This was signi - 

ficantly superior to the results of staged surgical palliation for this 

entity, for which the early mortality was as high as 50% at that 

time. 15 Nonetheless, mortality during waiting for transplantation 

has also been substantial, as high as 20%. The paradigm has shifted 

from primary transplantation to staged surgical palliation as a 

result of significant improvement in management and subsequent 

survival in patients with HLHS who undergo the Norwood pro - 

cedure and subsequent Fontan operation. 16 Primary heart trans - 

plantation for patients with HLHS is currently indicated in most 

of the centers when patients have severely reduced ventricular 

function, systemic atrioventricular valve insufficiency, and/or 

pulmonary valve abnormalities. 

Other CHDs that can make a patient a candidate for primary 

heart transplantation include pulmonary atresia with intact ven - 

tricular septum that has major coronary artery abnormalities, 

especially if the right ventricle–dependent coronary circulation is 

TABLE 105-3. Primary Diagnoses of Patients With 

Congenital Heart Disease Who Required Heart 

Transplantation 

Primary Diagnosis Number % 

Single ventricle not otherwise specified 22 21 

Tricuspid atresia 13 12 

HLHS/Sshone’s complex 12 11 

Double-inlet left ventricle 10 9 

D-Transposition of the great arteries 10 9 

Tetralogy of Fallot +/– pulmonary atresia 9 8 

Pulmonary atresia with intact ventricular 8 7 

septum 

L-Transposition of the great arteries 6 6 

Ebstein’s anomaly 3 3 

Other 13 12 

Adopted from Chen et al. Ann Thorac Surg. 2004;78:1252–1261. 13 

present. 17 Patients with heterotaxy syndrome, especially right 

isomerism, with a functional single ventricle and complex intra - 

cardiac and systemic and pulmonary venous abnormalities may 

be candidates for primary heart transplantation, considering that 

the outcomes of staged single-ventricle palliation have been ex - 

tremely poor. 18,19 Patients with any type of complex CHD with 

poor ventricular function and/or severe ventricular hypertrophy 

can be very high risks for corrective surgery and therefore might 

be candidates for primary heart transplantation. 

Heart Transplantation for Previously Repaired 

or Palliated Complex Congenital Heart Disease 

Patients who underwent two-ventricle repair for their CHD are 

less likely to be candidates for heart transplantation in the long 

term compared with patients who underwent staged singleventricle 

palliation. Some patients who have the right ventricle in 

the systemic position, that is, patients with D-transposition of the 

great arteries who underwent the atrial switch operation (Mustard 

or Senning procedure), or those with L-transposition of the great 

arteries who underwent physiologic repair, may have progressive 

right ventricular dysfunction and/or tricuspid valve regurgitation 

in the systemic circulation that may require heart transplan - 

tation. 20,21 Patients who received insufficient myocardial protection 

at the time of biventricular repair or had significant residual 

lesions that caused chronic volume and/or pressure overload to 

the systemic ventricle may be candidates for heart transplantation 

after two-ventricle repair. 

The Fontan operation or total cavopulmonary connection is 

the final physiologic status that patients with a functional single 

ventricle can possibly have. Major anatomic and physiologic 

factors that preclude the Fontan completion include poor ventri - 

cular function, significant systemic atrioventricular valve insuf - 

ficiency, increased fixed pulmonary vascular resistance (PVR), 

and unrepairable systemic and/or pulmonary venous abnormali - 

ties. If patients have such conditions during staged single-ventricle 

palliation, the Fontan operation is no longer indicated and heart 

transplantation is considered, although some conditions such as a 

significant increase in PVR may also preclude heart transplan - 

tation. 

Failing or Failed Fontan Physiology 

Since many patients have survived staged single-ventricle pallia - 

tion, a population that requires transplantation due to failing or 

failed Fontan physiology has been growing and has made up the 

largest single group of patients with CHD requiring heart trans - 

plantation. Even though patients achieved successful Fontan 

operations, there are several long-term issues that possibly com - 

promise Fontan physiology. Major indications for transplantation 

in this entity include progressive ventricular dysfunction, 

especially in patients with a right ventricle as a systemic chamber, 

elevated PVR, thromboembolism in the Fontan circuit, atrial 

and/or ventricular arrhythmias, protein-losing enteropathy, and 

persistent pleural effusion. Pretransplantation survival after listing 

is 78% at 6 months and 74% at 12 months. 22 This patient group 

may be the highest risk group for transplantation because of 

poor preoperative condition, potentially elevated PVR, previous 

multiple open-heart surgeries, and the need for a branch PA and/ 

or aortic arch reconstruction.


Retransplantation 

Retransplantation accounts for a small part of all the pediatric 

transplantations. It has made up approximately 1% of infant 

recipients and gradually increased in numbers to 7% of pediatric 

recipients. 1 Graft failure or posttransplant coronary vasculopathy 

is the major indication for pediatric retransplantation. 

Contraindications 

Absolute and relative contraindications to heart transplantation 

are listed in Table 105–4. The presence of human immunode - 

ficiency virus (HIV) infection has been an absolute contraindica - 

tion for heart transplantation; however, recent antiviral drug 

therapy may alter the natural history of this infectious disease. In 

fact, successful heart transplantation for adult patients with HIV 

infection has been reported. 23,24 Nonetheless, most centers includ - 

ing our center generally consider that HIV infection contraindi - 

cates heart transplantation in pediatric population. Active 

malignancy is an absolute contraindication for transplantation. 

Some controversies exist on indications for transplantation in 

patients who have a history of malignancy. Recent clinical ex - 

perience showed that cancer recurrence among patients who 

underwent heart transplantation for anthracycline-related car - 

diomyopathy is rare and warranted the reduction of the 5-year 

disease-free waiting period. 25 

Increased PVR that is not reactive to pulmonary vasodilation 

therapy is an absolute contraindication for surgery. Pulmonary 

vascular resistance greater than 4 Wood units used to be an absolute 

contraindication. Because of recent developments in pulmonary 

vasodilation agents and preoperative optimization strategies, 

consensus now is to consider PVR greater than 8 Wood units as an 

absolute contraindication. 

Relative contraindications include a history of poor drug 

compliance, lack of family support, and significant chromosomal, 

genetic, or extracardiac disorders. 

TABLE 105-4. Contraindications to Pediatric 

Heart Transplantation 

Absolute 

HIV infection 

Active malignancy 

Irreversible pulmonary hypertension 

Uncontrolled infection/sepsis 

Other organ failure 

Central nervous system dysfunction 

Significant neurodevelopmental disorder 

Severe stroke 

Significant psychiatric disorder 

Relative 

Poor compliance with medical regimen 

Prohibitive psychosocial circumstances (lack of family support) 

Chromosomal or genetic abnormalities 

Previous malignancy (


β-blockers may significantly improve cardiac function, allowing 

some children to be removed from the waiting list. 27 

Patients with severe acute heart failure or acutely decom - 

pensated heart failure should be treated more intensively. Intra - 

venous administration of inotropes, commonly dobutamine and/ 

or milrinone, systemic vasodilation therapy, and optimization of 

ventilation by noninvasive positive airway ventilation are the 

essential components of treatment. Endotrachial intubation is 

necessary if noninvasive ventilation does not improve symptoms 

and oxygenation. The effectiveness of β-blockers on acutely de - 

compensated heart failure depends on the patient’s ventricular 

condition. 

Systemic anticoagulation may be necessary in patients with 

severely reduced left ventricular function to prevent thrombus 

formation and subsequent thromboembolic events. Intravenous 

heparin, low molecular weight heparin, or coumadin are the 

agents of choice. 

Cardiac resynchronization results in significant clinical im - 

provement in some patients who have moderate-to-severe heart 

failure and an intraventricular conduction delay in adults. 28 None - 

theless, it is uncertain whether cardiac resynchronization therapy 

would benefit patients who are listed for transplantation. Place - 

ment of implantable cardioverter-defibrillators may be necessary 

in patients with cardiomyopathy and sustained ventri cular arrhy - 

thmias to prevent sudden death while waiting for transplan - 

tation. 29 

Medical management for patients with HLHS and its variant 

during the waiting period is particularly challenging. Primary 

focus is to balance systemic and pulmonary blood flow in the 

setting of ‘in-parallel’ circulation of HLHS. Systemic vasodilation 

therapy and/or mechanical ventilation in order to control PVR 

may be necessary to stabilize hemodynamics and to optimize 

systemic oxygen delivery. Arterial duct patency must be secured 

by continuous infusion of prostaglandin E 1 

. Stenting the arterial 

duct may be necessary for progressively restricting the duct despite 

prostaglandin therapy. Bilateral PA banding may also be necessary 

to mechanically restrict pulmonary blood flow. 30 The newly 

emerging hybrid palliation, that is, duct stenting and bilateral PA 

banding, seems to be an effective procedure as a palliative measure 

for bridging the gap to transplantation. 31 

Overall, mortality while waiting for transplantation is 17%. A 

small fragment of the remainder of the population (8%) recovers 

and the rest (63%) subsequently undergo transplantation. 26 The 

use of extracorporeal membrane oxygenation (ECMO), ventila - 

tory support, listing status 1A, CHD, and dialysis support are the 

risk factors for death during the waiting period. Mortality while 

waiting is somewhat high in patients with HLHS (25%), who 

mainly die as a result of heart failure (50%). 32 

Mechanical Circulatory Support: 

Bridge to Transplantation 

Mechanical circulatory support is indicated when a patient’s syste - 

mic cardiac output cannot be maintained by maximal medical 

therapy, including intravenous inotropes and mechanical ventila - 

tion. Current choices of devices include ECMO, the Thoratec VAD 

(Thoratec Corp, Pleasanton, CA), the EXCOR Berlin Heart (Berlin 

Heart AG, Berlin, Germany), and the MEDOS VAD (MEDOS 

Medizintechnik, AG, Stolberg, Germany). 33 Only the latter two 

devices are designed exclusively for children. 

Extracorporeal membrane oxygenation has been the primary 

device of choice in the pediatric population that requires biventri - 

cular support, especially in infants and/or children with complex 

CHDs. It can be initiated promptly via neck vessel cannulation 

and can support both circulation and oxygenation. Nonetheless, it 

is only designed for a short-term support of up to 2 weeks, and 

long-term ECMO-related complications may preclude transplan - 

tation. 34 In the Hospital for Sick Children, ECMO was used as a 

primary means of bridge to transplantation from 1990 to 2005 

until EXCOR Berlin Heart became available. Forty-six patients 

had been supported by ECMO. Mortality while waiting was 34% 

(16 out of 46%). Post-transplant survival of the patients who were 

supported by ECMO was 67% and 52% at 1 and 5 years, respec - 

tively. 35 Extracorporeal membrane oxygenation will still be the 

first-line device for neonates or small infants and patients with 

complex CHDs, especially those with single-ventricle anatomy 

who are not amenable to be supported by VAD. 

The multi-institutional study showed that 4% (99 out of 2375 

patients) of the patients who were listed for heart transplantation 

from 1993 to 2003 were supported by VAD. Pretransplant mor - 

tality was 17%. There were high rates of complications, including 

stroke (19%), bleeding (35%), and infection (35%). 

EXCOR Berlin Heart Ventricular Assist Device 

The EXCOR Berlin Heart VAD is the paracorporeal pulsatile 

device designed exclusively for pediatric use. Stroke volume ranges 

from 10 to 80 mL and the circuits are heparin-coated. The report 

from Deutsches Herzzentrum Berlin showed the successful bridge 

to transplantation or recovery rate of 68% in the recent experi - 

ences. 36 In The Hospital for Sick Children, Toronto, the EXCOR 

Berlin Heart VAD has been used as the first-line device bridging 

to transplantation since 2004. We electively implant biventricular 

assist devices in all cases because many children who are 

initially supported with left VAD subsequently develop right 

ventricular failure requiring mechanical support. Sixteen patients 

have been supported by EXCOR VAD. Pretransplant mortality 

during VAD support was 12% (2 patients) due to thromboembo - 

lism and sepsis. 

After a median sternotomy and systemic heparinization, 

standard cardiopulmonary bypass (CPB) is established by aortic 

and bicaval cannulations. The left ventricular apex is exposed and 

3-0 or 4-0 polypropylene sutures with pledgets (Ethicon, Inc, 

Somerville, NJ) are placed around a proposed cannulation site. A 

coin-sized incision corresponding to the cannula size is made and 

a left ventricular cannula is inserted. A side-biting vascular clamp 

is placed on the ascending aorta and a round hole is made. 

Pledgeted 4-0 polypropylene sutures are placed around the 

incision and are sewn to the aortic cannula. The same technique 

is used for the main PA cannulation. Finally, pled geted 4-0 

polypropylene sutures are placed on the right atrium, and the 

cannula is placed on the right atrium. The cannulas are tunneled 

through the abdominal fasciae and are connected to the pumps 

(Figure 105–1). Careful de-airing is performed before initiation 

of the pump support. Pump support is slowly started, and CPB is 

terminated. Heparin is carefully reversed by protamine administration. 

A Gore-Tex membrane (W.L. Gore & Associates, 

Flagstaff, AZ) is placed to cover the cannulas underneath the 

sternum to avoid cannula injury at chest reentry. The chest is 

routinely closed in the operating room. Anticoagulation, the 

continuous infusion of heparin, is started at 12 to 24 hours after 

operation once complete hemostasis is attained.


TABLE 105-6. Donor Inclusion and Exclusion Criteria 

Inclusion Criteria 

Declared brain death 

Freedom from active infection 

Heart: 

Structurally normal +/– minor abnormalities (e.g., patent 

foramen ovale) 

Reasonable cardiac function: 

left ventricular fraction shortening >25% 

left ventricular ejection fraction >40% 

Normal electrocardiogram 

ABO matched or compatible with potential recipient (recipient 

> 1 year old) 

Appropriately size-matched to potential recipient donor hearts 

up to three times greater in weight than that of the recipient 

Exclusion Criteria 

Figure 105-1. Configuration of Berlin heart EXCOR biventricular 

support. 

DONOR SELECTION CRITERIA 

AND MANAGEMENT 

Donor Selection 

Organ donors should be patients who have suffered irreversible 

brain death due to various injury processes such as traumatic brain 

injury or subarachnoid hemorrhage. Determi nation of brain death 

should be made with absolute certainty using accepted criteria. 37,38 

Inclusion and exclusion criteria of donor hearts are listed in Table 

105–6. Donor hearts should have reason able function without 

any evidence of significant ischemic myo cardial injury or mitral 

regurgitation. Donor hearts up to three times greater in weight than 

the recipient’s are generally accep table. Caution must be exercised 

when using infant donor hearts smaller than those of the recipient. 

Duration of cardiac arrest generally does not preclude eligibility 

for donation as long as cardiac function is reasonable. Sudden 

infant death syndrome (SIDS) in the donor is not a contraindication 

to donation if cardiac function is satisfactory. 

Impact of Brain Death on 

Hemodynamics and Metabolism 

Major hemodynamic changes induced by brain death include 

systemic hypertension caused by an increase in intracranial pres - 

sure inducing “catecholamine storm.” This phenomenon is usually 

temporary but significantly increases afterload to the potential 

donor heart. Both ventricles are severely dilated with significant 

pressure and volume overload. 39 Sudden increase in afterload may 

result in arrhythmias, myocardial ischemia, left ventricular failure, 

and secondary pulmonary edema. This may eventually lead to 

persistent decrease in vascular tone and hypotension. 

Does not meet brain death criteria 

Anencephaly (unless brain death present and all other criteria 

are met) 

Cardiac malformation other than 

simple patent ductus arteriosus 

simple atrial septal defect 

trivial ventricular septal defect 

trivial semilunar valve abnormalities 

Evidence of severe myocardial ischemic injury poor ventricular 

function without improvement with volume replacement and 

inotropes and/or 

left ventricular ejection fraction < 40% 

left ventricular fraction shortening < 25% 

mitral regurgitation 

Evidence of significant infection 

uncontrolled bacterial sepsis 

HIV positivity 

hepatitis B surface antigenemia 

hepatitis C positivity 

ABO incompatibility with potential recipient (if recipient 

> 1 year old) 

Inappropriate size match 

Adapted from Pediatric Heart Transplantation Protocol, Loma Linda 

International Heart Institute. 60 

Following brain death, free triidothyronine (T 3 

), thyroxine (T 4 

), 

cortisol, and insulin levels are reduced. Secondary reduction in 

glucose, pyruvate, and palmitate utilization result in the accu - 

mulation of lactate and free fatty acids, inducing a shift from 

aerobic to anaerobic metabolism. This shift in metabolism can be 

reversed by administering T 3 

. 40 

Donor Management 

Damage of the donor myocardium should be minimized during 

the period from brain death to the time of organ procurement. 

Myocardial injury due to catecholamine storm and subsequent 

increase in afterload can be minimized by afterload reduction 

therapy using nitroprusside and/or milrinone. Bradycardia and 

asystole during herniation are not responsive to atropine but 

isoproterenol or epinephrine can be effective. Blood pressure


should be maintained normally for age, and normal arterial pH 

and oxygenation should be sustained. Hydration to optimize 

intravascular volume status is essential to correct hypovolemic 

hypotension due to the loss of vasoregulatory function. Urine out - 

put should be maintained at a reasonable level. Diabetes insipidus 

due to insufficient secretion of antidiuretic hormone may result 

in massive diuresis, hypokalemia, and hypernatremia. If excessive 

urine output becomes an issue, vasopressin or desmopressin 

should be administered. Prophylactic antibiotics should be given 

before the retrieval. 

SURGICAL TECHNIQUES 

Donor Organ Procurement 

A median sternotomy is performed and the pericardium is 

opened. The heart is examined for any anomalies that may have 

been missed at the preoperative echocardiogram. Heparin (300 U/ 

kg) is administered intravenously. A cardioplegia cannula is 

inserted into the ascending aorta. Both ventricles should be totally 

decompressed before aortic cross-clamping. The inferior vena cava 

(IVC) is transected. The right pulmonary veins or left atrial 

appendage is incised as well. The aortic cross-clamp is placed and 

crystalloid cardioplegia (30 mg/kg, maximum 1 L) is administered 

through the aortic root. The myocardium is further protected by 

topical cooling. Care is taken to make sure that ventricles are not 

distended during cardioplegic administration. After completing 

cardioplegic administration, the heart is harvested. Depending on 

the recipient’s anatomy, the type of systemic venous anastomosis 

(biatrial or bicaval), and the reconstruction required (aortic arch, 

branch PAs), adequate margins of systemic and pulmonary veins 

and great vessels are secured. We routinely excise the superior vena 

cava (SVC) high up close to the innominate vein in order to create 

a large SVC anastomosis. If the recipient has a left SVC, the 

innominate vein should be harvested in situ in order to anasto - 

mose both SVCs. The main PA is excised just below the bifurca - 

tion. For the patients with HLHS or a failed Fontan procedure, 

branch PAs are harvested so that they can be used for branch PA 

reconstruction. The aorta is usually excised at the distal aortic 

arch. The neck vessels are transected about 1 cm from their origin. 

In cases of HLHS, the aortic arch is dissected and excised below 

the ductus ligamentum so that it can be used for aortic arch re - 

construction. If the lungs are supposed to be harvested, care is 

taken not to cut into the pulmonary veins or branch PAs and/or 

not to cut too close to the atrioventricular groove. The heart is 

stored in Ringer lactate in a series of sterile plastic bags and is 

placed in a protective plastic container to avoid mechanical injury. 

Unlike kidney and liver transplantation, graft function and 

survival following heart transplantation are generally considered 

to be decreased by an ischemic time of more than 4 to 5 hours. 

Nonetheless, recently clinical study showed that a prolonged 

ischemic time of more than 8 hours does not affect long-term graft 

survival. 41 

Recipient Operation 

A median sternotomy is performed. After systemic heparinization, 

CPB is initiated with ascending aortic and bicaval cannulations. 

Mild hypothermia is induced. Heart transplantation for complex 

CHDs often requires deep hypothermic circulatory arrest, for 

which further cooling is performed. The aorta is cross-clamped, 

and the heart is excised. The right atrium is incised and the 

incision is extended along the atrioventricular groove. The aorta 

and the PA are excised at their valves. If bicaval anastomosis is 

performed (our preferred approach), the right atrial wall is excised 

and the SVC and IVC are trimmed. Both atrial appendages are 

excised. The donor heart is inspected and trimmed. The atrial 

septum should be inspected before starting anastomosis. Patent 

ovale foramen should be closed if any. The donor heart is placed 

on the left side of the mediastinum. The left atrial anastomosis is 

first made starting at the base of the left atrial appendages using a 

long 4-0 or 5-0 polypropylene suture. A vent tube is placed in the 

left atrium via the suture line until releasing the aortic cross-clamp. 

The donor main PA is shortened as much as possible to avoid 

possible kinking. The PA anastomosis is made with a fine poly - 

propylene suture, such as a 6-0 suture. Care is taken not to pursestring 

the suture line, which potentially causes stenosis. The donor 

aorta is usually left relatively long, and the aortic anastomosis is 

made typically with a 5-0 polypropylene suture. The left atrial 

anastomotic suture is tied, and the venting tube is removed. After 

appropriate de-airing, the aorta is declamped. While the heart is 

beating, the IVC anastomosis is made using a relatively large 

suture, such as 4-0 polypropylene suture. Finally, the SVC 

anastomosis is made using a fine suture, such as 6-0 or 7-0 

polypropylene suture. Our preferred technique is to use a running 

suture technique on the back wall of the SVC and to use inter - 

rupted stitches on the anterior wall to minimize the risk of SVC 

stenosis. If the patient is a neonate or small infant, a biatrial 

anastomosis technique is used to minimize the risk of caval 

obstruction. 

Left Superior Vena Cava 

If the recipient has a left SVC, there are two techniques to handle 

this issue. If the left SVC drains into the coronary sinus, the 

recipient cardiectomy can be altered in a way that the left SVC 

continues to drain via the recipient coronary sinus into the new 

atrium. Subsequent biatrial anastomosis allows left SVC drainage 

to drain into the new right atrium via the coronary sinus. 

Alternatively, the donor innominate vein is used to reconstruct 

the left SVC. This technique allows bicaval anastomosis with an 

additional left SVC–innominate vein anastomosis. 

Hypoplastic Left-Sided Heart Syndrome 

The aortic arch, ductus arteriosus, and branch PAs are dissected 

out. The neck vessels are dissected and taped for circulatory arrest. 

Cardiopulmonary bypass is established with the main PA and 

bicaval cannulations. A single venous cannulation on the right 

atrium is applied when operating on neonates with small SVCs. A 

patient is cooled down to 18 degrees, typically for 20 minutes. The 

heart is excised (Figure 105–2A). The left atrial anastomosis is 

made with a 5-0 polypropylene suture (Figure 105–2B). Deep 

hypothermic circulatory arrest is commenced. The aortic incision 

is extended into the descending aorta beyond the duct-inserted 

site, that is, the coarctation site. The aortic arch reconstruction is 

made using the donor aortic arch using 7-0 or 6-0 polypropylene 

suture. Selective cerebral perfusion of approximately 30% of 

total pump flow is commenced if a bloodless field is secured. Pul - 

monary artery anastomosis is made in a standard manner unless 

the patient has had previous bilateral PA banding as a palliative 

procedure, for which bilateral branch PA plasty with donor branch


A 

C 

B 

PAs may be required. The aorta is declamped and the patient is 

rewarmed. The right atrial anastomosis (our preferred approach 

for neonates and small infants) is performed in the beating state 

during rewarming, completing the anastomoses (Figure 105–2C). 

The chest may have to be left open, especially when the donor 

heart is considerably larger than the recipient’s. 

Transplantation for Failed or Failing 

Fontan Procedure 

Heart transplantation for failed Fontan physiology involves exten - 

sive reconstruction of branch PAs and/or the aortic arch. Patients 

with failed Fontan physiology undergoing heart transplantation 

should be brought to the operating room earlier than standard 

cases because severe adhesions are expected as a result of multiple 

previous operations. After the dissection, CPB is initiated with 

ascending aortic and bicaval cannulation. Caval cannulations 

should be placed as distal as possible in cases requiring plasty of 

Figure 105-2. Surgical techniques in heart transplantation 

for patients with hypoplastic left-sided heart syndrome. A: 

Anatomy and incisions. The ductal tissue is completely removed. 

The aortic arch is incised all the way down to the descending 

aorta beyond the duct-inserted site. The main pulmonary artery 

is excised just underneath the bifurcation of branch pulmonary 

arteries. B: The beginning of anastomosis. The left atrial anastomosis 

is started at the base of the left atrial appendage. C: Completion 

of anastomosis. The aortic arch is reconstructed with the 

donor aortic arch. 

caval anastomosis. Moderate to deep hypothermia is induced for 

possible deep hypothermic circulatory arrest for PA and/or aortic 

arch reconstruction. Failed Fontan patients frequently have 

multiple collateral vessels, which makes establishment of a 

bloodless field difficult. The heart is excised. The sequence of 

anastomosis is similar to that of standard transplantation. The 

branch PAs are typically reconstructed by the donor branch PAs. 

If the aorta is abnormally dilated (typically as a result of a previous 

Norwood type operation), the aortic arch reconstruction is 

sometimes necessary (techniques described in “Hypoplastic Left- 

Sided Heart Syndrome”). 

Intraoperative Medical Management 

Cardiopulmonary bypass is terminated with chronotropic (isopre - 

naline) and/or inotropic (epinephrine) supports. A phosphdieste - 

rase inhibitor (milrinone) is routinely used. Temporary pacing 

wires are placed and the heart is paced at an adequate heart rate.


Central venous pressure is maintained at less than 10 to 12 mmHg 

to avoid excessive volume overload to the right ventricle and 

subsequent right ventricular dilatation. Transesophageal echocar - 

diography is routinely performed. Biventricular function, especi - 

ally right ventricular function, estimated right ventricular systolic 

pressure, the presence or absence of semilunar valve and atrioven - 

tricular valve insufficiencies, and the presence or absence of 

anas tomotic stenosis are evaluated. Pulmonary hypertension is 

managed with nitric oxide inhalation. The chest is left open in 

neonates or infants with a large donor heart with or without right 

ventricular dysfunction. Postoperative management and immuno - 

suppression therapy are not discussed in this chapter. 

CLINICAL OUTCOMES 

A recent report from the Pediatric Heart Transplant Study Group 

showed that overall actuarial survival after transplantation for all 

age groups is 85% at 1 year and 75% at 5 years. Survival among 

infants less than 6 months old is 82% at 1 year and 66% at 10 

years. 42,43 There is a trend toward improving outcome in transplan - 

tation over time from 5-year survival of 72% for the era from 1993 

to 2000 to 77% for the years from 2001 to 2005. Survival after 

transplantation among the patients who had failed Fontan 

physiology is 76% at 1 year and 68% at 5 years. Protein-losing 

enteropathy in those patients can be resolved after transplantation. 

SPECIAL CONSIDERATIONS 

ABO-Incompatible Transplantation 

Neonates have an immature immune system and both humoral 

and cellular immunity are suppressed. Neonates and young infants 

have been described as presenting less aggressive immune reac - 

tions to foreign transplanted tissue until 3 months of age. Neonates 

also do not produce anti-A or anti-B antibodies until 5 to 6 

months of age, with titers gradually increasing up until 2 years of 

age. Antibody production may occur earlier if there is sufficient 

antigenic stimulation, such as the presence of A and/or B antigens 

on a heart graft. Antibody present in the serum from birth is 

maternally derived IgG, typically present in low titers. The im - 

maturity of the infantile immune system led us to initiate an ABOincompatible 

heart transplantation program. 

In The Hospital for Sick Children, since 1996, parents of fetuses 

and infants who are candidates for heart transplantation have been 

offered the heart from the first available donor of compatible size, 

regardless of blood type. 44 All patients on the transplant list are 

tested periodically for the presence of anti-A or anti-B antibodies. 

Once a potential donor is identified, serum antibody testing is 

repeated immediately. The recipient’s antibody titer level is 

quantified preoperatively. An exchange transfusion of the recipient 

is performed at the initiation of CPB to reduce the concentration 

of circulating antibody level to blood group antigens to an 

undetectable level. 45 The patient’s blood is drained into a separate 

bag while transfusing the primed volume at initiation of CPB. The 

volume of exchanged plasma is equal to three times the estimated 

blood volume (80 mL/kg). Red blood cells used in priming are 

ABO-compatible with the recipient. All plasma components do 

not contain anti-A or anti-B antibodies to donor or recipient 

(Table 105–7). To ensure the effectiveness of exchange transfusion, 

anti-A and anti-B antibody titers are sent to the laboratory for level 

determination at 10 minutes on CPB, prior to aortic cross-clamp 

removal, and at the termination of CPB. Exchange transfusion is 

repeated as necessary to maintain low titers. 

All infants receive 20 mg/kg of methylprednisolone at the 

induction of anesthesia and before the release of the aortic crossclamp. 

An infusion of rabbit polyclonal antilymphocyte prepara - 

tion is started at induction and runs for 2 to 7 days, adjusted to 

yield a lymphocyte count of 200 to 400 per mm. 44 Primary im - 

munosuppression consists of a triple drug therapy: steroids, 

tacrolimus, and mycophenolate mofetil (MMF). 

The initial experience in the Hospital for Sick Children that 

consisted of 10 infants from 1996 to 2000 showed early survival of 

80%. Two early deaths were not related to ABO-incompatibility. 

The recent multi-institutional study based on the United Network 

for Organ Sharing database showed that 35 (6%) patients out of 

591 patients who were less than 1 year of age underwent ABOincompatible 

heart transplantation from 1999 to 2007. 46 There was 

no difference in survival between the groups (70% at 1 year for 

both groups) or incidence of hyperactive rejection (one in in - 

compatible group vs. two in compatible group). Another multiinstitutional 

study from England showed no hospital mortality 

among 21 patients who underwent ABO-incompatible heart 

transplantation from 2000 to 2006. 47 

Heart Transplantation from Donation 

After Cardiocirculatory Death 

Donation after cardiocirculatory death (DCD), which was used to 

refer to “non–heart-beating-donors,” has been proposed as a 

means to expand the donor pool for heart transplantation in the 

TABLE 105-7. Blood Group Compatibility When Administering Blood Products During an ABO-Incompatible 

Heart Transplantation 44 

Donor’s Blood Group Recipient’s Blood Group Indicated Blood Group 

Plasma PRBC Platelets 

AB O AB O AB 

B O AB or B O AB or B 

A O AB or A O AB or A 

AB B AB O or B AB 

A B AB O or B AB 

AB A AB O or A AB 

B A AB O or A AB 

PRBC = packed red blood cells


face of significant donor shortage and substantial mortality during 

waiting for transplantation, especially in infants. 26 In fact, the first 

successful heart transplantation in an adult involved a donor who 

died from cardiocirculatory death. 48 Although attractive, this stra - 

tegy has stayed within laboratory medicine up until very recently 

because of substantial hypoxic myocardial injury during the 

agonal period and reperfusion injury after a long warm ischemic 

period. The Loma Linda group has published a landmark animal 

study looking at the possibility of pediatric heart transplantation 

from DCD. 49 The study showed that the animals survived as long 

as 34 days after as long as 30 minutes of warm ischemia with 

reasonable left ventricular ejection fraction (mean 76%). 49 Nume - 

rous experimental studies have been performed on this particular 

subject focusing on myocardial protection; however, many of 

those studies involved multiple premedications before withdrawal 

of care, which limits clinical application of those strategies. 50 The 

Denver group recently published their experience of three pedi - 

atric heart transplantations from DCD. The protocol indicates that 

if death occurs within 30 minutes after extubation, the patient is 

considered to be a candidate for donation. The mean time of 

donors was 3.7 days. All donors suffered birth asphyxia as a cause 

of death. Extubation was performed after heparin (100 U/kg) 

administration and sedation and analgesia (fentanyl and loraze - 

pam). The mean time to death after withdrawal of life support was 

18 minutes (11 to 27 minutes). When cardiocirculatory function 

ceased, the patients was observed for 3 minutes (the first patient) 

or 75 minutes (the rest) and the organ donation process was 

initiated with the administration of cold cardioplegia into the 

aortic root through the long balloon catheter placed in the 

ascending aorta. The 6-month survival time was 100% compared 

to 84% in 17 control patients in the same period. There were no 

late deaths. These three patients had reasonable left ventricular 

systolic function at 6 months and a similar number of rejection 

episodes compared to controls (0.3 per patient versus 0.4 per 

patients in controls). The first clinical experience is indeed 

encouraging but still holds some medical and/or ethical issues to 

be overcome. One of the major issues is the duration between the 

declaration of cardiocirculatory death and organ retrieval. A 1997 

report from the Institute of Medicine suggested that 5 minutes 

should elapse between cardiocirculatory death and organ retrie - 

val. 51 The second report from the Institute of Medicine in 2000 

reassessed the time interval and stated that the empirical data 

available indicate that cardiopulmonary arrest becomes irrever - 

sible within a shorter time interval—60 seconds or less. 52 On the 

basis of this report, the Denver group used 75 seconds as the 

duration from death to retrieval; however, no scientific data have 

yet been elucidated to support this practice. Pediatric heart 

transplantation from DCD seems to be feasible, but graft preser - 

vation technique, long-term graft function, and ethical issues 

including time interval from declaration of death to retrieval 

should be well discussed and established before regular clinical 

application. 

Management of Highly Sensitized Patients 

Undergoing Heart Transplantation 

Some patients awaiting heart transplantation have circulating 

antibodies against human leukocyte antigens (HLA). The process 

by which antibodies are formed is called sensitization. Sensitiza - 

tion may result from previous blood transfusion, 53 homograft 

materials used for reconstruction in congenital heart surgery, 54 or 

use of mechanical circulatory assist devices. 55 Patients who require 

retransplantation often have allosentization. 56 There has been an 

increase in heart transplant candidates who have been allosensi - 

tized to HLA antigens over the years. The recent study showed 

that panel-reactive antibody (PRA) higher than 25% is associated 

with poor survival after heart transplantation. 57 Recent experience 

showed that 13 (8%) out of 167 patients who had undergone trans - 

plantation from 1990 to 2006 met the criteria for being allosensi - 

tized before heart transplantation, characterized by a PRA greater 

than 10%. 58 Nine (69%) were infants who had had previous 

palliation for CHD. Antibody-mediated rejection occurred in 

9 (69%) patients and acute cellular rejection (>ISHLT Grade 2 R) 

occurred in 7 (53%) patients, which seems more frequent than a 

regular transplant group. The actuarial survival at 1 year was 71%. 

Pretransplant treatment includes weekly intravenous administra - 

tion of immune globulin or an oral low dose of MMF (20 mg/ 

kg/d) in an attempt to reduce circulating alloantibodies. Perio - 

perative management includes plasma exchange during transplan - 

tation as described above and induction of thymoglobulin. Most 

recently, rituximab, an anti-CD20 monoclonal antibody that 

rapidly causes destruction of CD20 positive cells, has been used 

empirically perioperatively. Postoperative management includes 

induction therapy with thymoglobin (1.5 mg/kg/day) for 2 to 7 

days and standard triple immunosuppression with tacrolimus, 

MMF, and steroid. 

In summary, current practice in pediatric heart transplantation 

has attained reasonable early and long-term survival and graft 

function in all subsets of patients with end-stage heart failure. 

Ventricular assist device as a means of bridge to transplantation, 

ABO-incompatible transplantation, and possibly transplantation 

from DCD are the key practices to improve overall outcomes by 

reducing mortality while awaiting transplantation or by improving 

the preoperative condition of such patients. High pretransplant 

mortality, management of the growing number of transplantations 

for failed Fontan procedure patients, and the sensitization issue 

have to be overcome. 

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