Tetralogy of Fallot

Summary

Tetralogy of Fallot is the most common form of cyanotic congenital heart disease, and one of the first to be successfully repaired by congenital heart surgeons. Since the first procedures in the 1950s, advances in the diagnosis, perioperative and surgical treatment, and postoperative care have been such that almost all those born with tetralogy of Fallot can now expect to survive to adulthood. The startling improvement in outcomes for babies born with congenital heart disease in general—and for those with tetralogy of Fallot in particular—is one of the success stories of modern medicine. Indeed, in many countries adults with tetralogy of Fallot outnumber children. Consequently, new issues have emerged, ranging from hitherto unpredicted medical complications to issues with training for caregivers and resource allocation for this population of survivors. Therefore, evolution of treatment, recognition of late complications, research on disease mechanisms and therapies—with feedback to changes in care of affected children born nowadays—are templates on which the timely discussion of organisation of care of those affected by congenital heart diseases from the fetus to the elderly can be based. Here, we focus on new developments in the understanding of the causes, diagnosis, early treatment, and late outcomes of tetralogy of Fallot, emphasising the continuum of multidisciplinary care that is necessary for best possible lifelong treatment of the 1% of the population born with congenital heart diseases.

Introduction

Tetralogy of Fallot was first described by Niels Stenson in 1671, although its precise anatomical description was elegantly illustrated by William Hunter at St Georges Hospital Medical School in London in 1784: “…the passage from the right ventricle into the pulmonary artery, which should have admitted a finger, was not so wide as a goose quill; and there was a hole in the partition of the two ventricles, large enough to pass the thumb from one to the other. The greatest part of the blood in the right ventricle was driven with that of the left ventricle into the aorta, or great artery, and so lost all the advantage which it ought to have had from breathing”.1, 2 His description of a large outlet ventricular septal defect together with subpulmonary and pulmonary valve stenosis, and its resulting physiology, was refined by Etienne-Louis Fallot in 1888 in his description of L'anatomie pathologique de la maladie bleu, but the term tetralogy of Fallot (a tetrad of (i) ventricular septal defect with (ii) over-riding of the aorta, (iii) right ventricular outflow obstruction, and (iv) right ventricular hypertrophy) is attributed to Canadian Maude Abbott in 1924.

We now regard tetralogy as a family of diseases, all characterised by a similar intracardiac anatomy (figure 1), but highly variable in terms of pulmonary artery anatomy, associated abnormalities, and outcomes. Here, we focus on the most common form, in which the heart has normal segmental anatomical structure, the right ventricular outflow tract is patent at birth, and no other major intracardiac abnormalities, such as atrioventricular septal defect, exist.

About 3·5% of all infants born with a congenital heart disease have tetralogy of Fallot, corresponding to one in 3600 or 0·28 every 1000 livebirths, with males and females being affected equally.³ Its precise cause is unknown, as for most congenital heart diseases. Most cases seem sporadic, although the risk of recurrence in siblings is about 3% if there are no other affected first-degree relatives.

However, a strong and increasingly recognised genetic substrate to tetralogy can affect the outcome after surgical repair.⁴ One study showed that a microdeletion of the q11 region of chromosome 22 was present in up to 25% of patients, suggesting that investigation with fluorescent in-situ hybridisation for such a deletion should be undertaken in all patients when diagnosed.⁵ Indeed, tetralogy is closely associated with, and frequently diagnosed in those with, overt Di George syndrome or velocardiofacial syndrome, both of which have 22q11 deletions.6, 7 In those without an overt syndrome, the prevalence of deletions has been estimated at 6%.⁸ 22q11 deletion is becoming increasingly important not only because of its cardiac and syndromic associations, but also because of its association with late-onset neuropsychiatric disorders. Bassett and colleagues⁹ showed that adults with 22q11.2 deletion syndrome have a rate of schizophrenia of almost 25%; about 1% of patients with schizophrenia therefore have an associated 22q11.2 deletion.¹⁰