eMedicine Specialties > Pediatrics: Surgery > Transplantation

Heart Transplantation

Author: Richard E Chinnock, MD, Medical Director of Pediatric Heart Transplant Program, Professor and Chair, Department of Pediatrics, Loma Linda University School of Medicine and Children's Hospital
Contributor Information and Disclosures

Updated: Nov 7, 2008

Introduction

Heart transplantation in infants and children is now accepted therapy. Survival in excess of 20 years after pediatric heart transplantation has been achieved. Most programs now report that more than 70% of their recipients survive at least 5 years. However, although an additional 5 years of life is important for all, the goal of pediatric heart transplantation is to provide as much of a normal life span for these children as possible. This article describes the unique aspects of heart transplantation as applied to infants and children.

History of the Procedure

The first pediatric heart transplantation was performed in 1968 when the heart of an infant with anencephaly was transplanted into an 18-day-old infant with Ebstein anomaly. This neonate died 5 hours after the procedure. Older children occasionally underwent transplants during the 1970s and early 1980s at Stanford University. Successful routine cardiac transplantation began after the introduction of cyclosporine. Its successful application to infant recipients began in 1985.

Problem

An estimated 10% of congenital heart disease cases have been deemed uncorrectable. One of the most common indications for infant heart transplantation had been hypoplastic left heart syndrome (HLHS), which occurs in about 1 in 6,000 live births. HLHS has diminished as an indication for heart transplantation because of inadequate donor supply and improvement in the surgical palliative approach (ie, the Norwood procedure, with or without the Sano modification). Congenital malformations are still the most common indication for infant heart transplantation. Congenital cardiomyopathy occurs in approximately 1 in 10,000 live births.

The most common indication for heart transplantation in older children is cardiomyopathy. The number of children who have failing cardiac function late after palliative surgery for congenital heart disease is increasing. An important example is the so-called failed Fontan.

Frequency

According to the registry of the International Society for Heart and Lung Transplantation, approximately 350-400 pediatric heart transplantation procedures are performed worldwide each year, representing about 10% of the total number of heart transplants performed.1

Etiology

The 4 etiologies that lead to conditions that might require heart transplantation include errors in the formation of the heart, cardiac tumors, infections, and toxins (either endogenous or exogenous) that lead to damage to the myocardium. Many of the congenital anomalies, including congenital cardiomyopathy, are now known to have specific associated chromosomal abnormalities. An example is the so-called "Catch-22" syndrome, a 22q11 band deletion associated with DiGeorge syndrome and interrupted aortic arch.

Conditions considered for pediatric heart transplantation include the following:

Pathophysiology

The pathophysiology of conditions that require heart transplantation is obviously as varied as the conditions themselves. However, the underlying principle of the inability of the pump to supply adequate perfusion for end-organ health and well-being is inherent in each condition.

Heart failure in pediatric heart disease is staged from A to D.

  • Stage A = At risk for developing heart failure
  • Stage B = Abnormal cardiac structure and/or function but no symptoms of heart failure
  • Stage C = Abnormal cardiac structure and/or function and past/present symptoms of heart failure
  • Stage D = Abnormal cardiac structure and/or function, requiring continuous infusion of intravenous inotropes or prostaglandin E 1 (to maintain patency of the patent ductus arteriosus) or requiring mechanical ventilatory and/or mechanical circulatory support.

Details of the pathophysiology of each condition can be obtained from the appropriate eMedicine articles.

Presentation

Infants with serious congenital heart disease generally present in the newborn period with varying degrees of cyanosis, tachypnea, tachycardia, dysrhythmias, poor perfusion, feeding intolerance, and other symptoms of heart failure. Symptoms of heart failure, either rapid or slow onset, are associated with the cardiomyopathies. Children with tumors may present with congestive heart failure (CHF) or with syncope or cardiac arrest due to arrhythmias. Specific presentations for each of the diagnoses can be found in the appropriate eMedicine articles.

An increasing number of congenital lesions are diagnosable based on fetal ultrasonography findings.

Indications

Heart transplantation may be indicated in various conditions.

Dilated cardiomyopathy

Guidelines about specific hemodynamic, echocardiographic, and clinical criteria that indicate the advisability of cardiac transplantation are not yet established. The risk of death is highest during the first 3 months after presentation, so decisions regarding transplantation should be made relatively soon after diagnosis. Risk factors for poor outcome include children older than 5 years at the time of presentation, familial cardiomyopathy and endocardial fibroelastosis, severe persistent depression of left ventricular systolic function (shortening fraction <0.12 and ejection fraction <0.20), severe mitral regurgitation, persistent left ventricular end-diastolic pressure greater than 20 mm Hg, mural thrombus on echocardiogram, globular (rather than elliptical) left ventricular shape, and the presence of complex atrial and ventricular arrhythmias. Any child who presents with these risk factors should be considered for early referral for transplantation.

Hypertrophic cardiomyopathy

Clinical presentation widely varies, as does the natural history. Risk factors for poor prognosis include a presentation in infancy, syncopal symptoms, family history of progressive hypertrophic cardiomyopathy, sustained ventricular tachycardia, mitral regurgitation, and development of atrial fibrillation. Heart transplantation is generally reserved for patients who are symptomatic and who have either multiple risk factors for poor survival or impaired systolic function marking the onset of advanced stages of disease.

Restrictive cardiomyopathy

In children, survival rates are generally poor, with a median time from diagnosis to death of about 1 year. A tendency for a progressive increase in pulmonary vascular resistance also exists. Early referral for cardiac transplantation is indicated.

Anatomically uncorrectable congenital heart disease

These lesions include any cardiac malformation for which a 2-ventricle repair is not possible or advisable. Cardiac transplantation is recommended for certain subsets with poor short-term or intermediate survival rates.

A special case is the infant with hypoplastic left heart syndrome (HLHS). The current recommended options include a series of palliative operations that lead to a later Fontan procedure (also called the Norwood operation) and cardiac transplantation. Each operation has pros and cons. The staged surgical repair requires multiple operative procedures and ends with single ventricle physiology. Transplantation requires life-long immunosuppression. Both options are palliative. Both options, in all likelihood, eventually lead to transplantation or retransplantation in the child's future.

For all patients considered for the Fontan pathway, cardiac transplantation should be considered a more appropriate therapy if the Fontan mortality rate is expected to be 20% or greater. Factors that increase the Fontan mortality rate include significant systemic atrioventricular (AV) valve insufficiency, moderate (but not severe) elevation of pulmonary vascular resistance, and depressed systemic ventricular function.

Conditions at high risk for corrective operation

Patients with potentially correctable congenital heart disease who are at greatly increased operative risk should also be considered for transplantation. This decision somewhat depends on the surgical results at specific institutions. Lesions that should be considered include complex truncus arteriosus (with severe truncal valve insufficiency, interrupted aortic arch, or coronary artery anomalies), some severe forms of Shone complex, and complex interrupted aortic arch.

Cardiac tumors

Primary cardiac tumors rarely metastasize; therefore, transplantation is not contraindicated. Transplantation is indicated if the tumor is unresectable and is confined to the portion of the heart removed at transplantation; major associated congenital anomalies must not be present. In children with tumors associated with tuberous sclerosis, spontaneous regression is common. Transplantation should be considered if severe left ventricular outflow obstruction, hemodynamic compromise, or life-threatening arrhythmias are present.

The American Heart Association recently published recommendations for the indications for heart transplantation in children.2

Relevant Anatomy

Anatomic considerations in heart transplantation are diverse and should be reviewed according to the particular condition.

Abnormalities of situs, systemic venous return, and malpositions of the great vessels can be surgically managed at the time of cardiac transplantation.

Contraindications

Some anatomic considerations specifically referable to transplantation exist. The major anatomic contraindication is small pulmonary arteries that cannot be satisfactorily surgically enlarged. Other features that could preclude safe heart transplantation include subsets of anomalous pulmonary venous connection without a suitable pulmonary venous confluence for direct anastomosis to the donor left atrium.

Pediatric heart transplantation has few absolute contraindications. Many children who are quite ill can make a remarkable recovery once a new heart restores adequate perfusion. However, the following are considered incompatible with successful transplantation:

  • Irreversible elevated pulmonary vascular resistance (>6 Wood units per m2 and/or a transpulmonary gradient >15 mm Hg)
  • Diffuse hypoplasia of the central branch pulmonary arteries
  • Total anomalous pulmonary venous connection without pulmonary venous confluence
  • Ectopia cordis
  • Active systemic infection
  • Infection with human immunodeficiency virus (HIV) or chronic active hepatitis B or C
  • Malignancy without cure or of recent onset
  • Severe primary renal or hepatic dysfunction
  • Multiorgan system failure
  • Major CNS abnormality
  • Severe dysmorphism
  • Marked prematurity (<36 wk)
  • Small size (<1800 g)
  • Positive finding on drug screen
  • Lack of family support systems

More on Heart Transplantation

Overview: Heart Transplantation
Workup: Heart Transplantation
Treatment: Heart Transplantation
Follow-up: Heart Transplantation
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

heart transplantation, cardiac transplantation, hypoplastic left heart syndrome, HLHS, congenital cardiomyopathy, errors in the formation of the heart, cardiac tumors, infections, toxins, cyanosis, tachypnea, tachycardia, dysrhythmias, poor perfusion, feeding intolerance, heart transplant, Ebstein anomaly, Catch-22 syndrome, DiGeorge syndrome, interrupted aortic arch, dilated cardiomyopathy, restrictive cardiomyopathy, hypertrophic cardiomyopathy, pulmonary atresia with intact ventricular septum, transposition of the great arteries, heart block, atrioventricular septal defect, heart failure, cyanosis, tachypnea, tachycardia, dysrhythmias, poor perfusion, feeding intolerance, cardiac arrest

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Contributor Information and Disclosures

Author

Richard E Chinnock, MD, Medical Director of Pediatric Heart Transplant Program, Professor and Chair, Department of Pediatrics, Loma Linda University School of Medicine and Children's Hospital
Richard E Chinnock, MD is a member of the following medical societies: American Academy of Pediatrics, American Heart Association, American Medical Association, American Society of Transplantation, California Medical Association, International Society for Heart and Lung Transplantation, Society for Pediatric Research, Transplantation Society, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Richard G Ohye, MD, Director, Pediatric Cardiac Transplantation, Fellowship Program Director, Pediatric Cardiac Surgery, Assistant Professor, Department of Surgery, Section of Cardiac Surgery, University of Michigan Medical Center
Richard G Ohye, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Chest Physicians, American College of Surgeons, Association for Academic Surgery, International Society for Heart and Lung Transplantation, and Society of Thoracic Surgeons
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Steve Dunn, MD, Chief, Solid Organ Transplantation, Department of Surgery, Alfred I DuPont Hospital for Children at Wilmington
Steve Dunn, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, American Society of Transplant Surgeons, American Society of Transplantation, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

CME Editor

Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College
Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Associate Professor, Department of Pediatrics, Baylor College of Medicine
Steven R Neish, MD, SM is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and American Heart Association
Disclosure: Nothing to disclose.

 
 
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