Download The Adult With Congenital Heart Disease

Journal of the American College of Cardiology
© 2005 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 46, No. 1, 2005
ISSN 0735-1097/05/$30.00
doi:10.1016/j.jacc.2005.02.083
STATE-OF-THE-ART PAPER
The Adult With Congenital Heart Disease
Born to Be Bad?
Carole A. Warnes, MD, MRCP, FACC
Rochester, Minnesota
The population of patients with adult congenital heart disease is approximately 800,000 in the
U.S. Those with prior cardiac surgery often consider themselves “cured,” although the
majority faces a lifetime of problems including arrhythmias, ventricular dysfunction, and one
or more re-operations. Even patients with repaired “simple” lesions such as an atrial septal
defect may not have normal survival if they are repaired in adulthood. Patients with repaired
coarctation may have premature cardiovascular complications including sudden cardiac death,
myocardial infarction, and stroke. They also have aortic complications such as aneurysm and
dissection, which result from a diffuse arteriopathy and continued hypertension that may be
caused by underlying endothelial dysfunction. In addition, bicuspid aortic valve occurs in
more than one-half of the patients with coarctation, so continued surveillance for significant
aortic valvular heart disease is necessary. More complex lesions also pose problems after “total
correction.” Patients with repaired tetralogy of Fallot often have pulmonary regurgitation,
which is frequently overlooked on clinical exam and echocardiography. Pulmonary valve
replacement should be performed before the development of irreversible right ventricular
dysfunction and an increased risk of ventricular tachycardia or sudden cardiac death. Because
they are vulnerable to deterioration of systemic ventricular function, those with congenitally
corrected transposition require special vigilance, usually with concomitant atrio-ventricular
valve regurgitation. Late referral is common with a deleterious effect on long-term survival.
These patients need lifelong follow-up and the residua and sequelae of their complex
anomalies must be understood in order to provide optimum care. (J Am Coll Cardiol 2005;
46:1– 8) © 2005 by the American College of Cardiology Foundation
The last 50 years have witnessed dramatic changes for the once
threatened and limited life of the baby born with congenital
heart disease. The advances in echocardiography, anesthesia,
intensive care, and particularly cardiac surgery have facilitated
the survival of babies born with even the most complex cardiac
anomalies. Fifty years ago, only 25% of these infants would
survive beyond the first year of life, but now more than 95%
will survive to adulthood. This triumph of survival, which has
evolved over the last few decades, has led to a “new population”
of adults with congenital heart disease. This population size is
estimated to be approximately 800, 000 in the U.S. (1).
Some patients may have mild defects and have never needed
surgery; in others, the defect may have been missed and may
not be discovered until adulthood. The majority, however, have
had previous cardiac surgery and may consider themselves
“cured.” The perception of “cure” is fostered by the surgical
description “total correction,” which is applied to many operative repairs of complex congenital anomalies. In reality, there
is almost no surgical cure for congenital heart disease, perhaps
with the exception of a successfully ligated and divided ductus
arteriosus. All other repaired lesions have the potential for
residua and sequelae, and although this may be a painful
realization for patients and their families, it is a fundamental
From the Division of Cardiovascular Diseases and Pediatric Cardiology, Mayo
Clinic College of Medicine, Rochester, Minnesota.
Manuscript received February 6, 2005; revised manuscript received February 15,
2005, accepted February 22, 2005.
and important concept. The misperception of “cure” has
potentially serious consequences. Patients may forget to use
antibiotic prophylaxis, are unlikely to endeavor to understand
the nature of their anomaly, and, much more importantly, see
no need to seek continued medical advice. As a result, residual
lesions and sequelae are frequently overlooked until patients
present with symptoms.
These patients are different from those with acquired heart
disease. One of the most common presentations is with an
arrhythmia, and cardiologists unfamiliar with congenital heart
disease often focus on the electrophysiologic aspects of the
symptom complex, unaware of the underlying hemodynamic
problems so commonly associated with the onset of arrhythmias. In contrast to patients with acquired heart disease, who
usually notice a distinct change in symptoms at the onset of
their problems, patients with congenital heart disease, having
lived with a lifelong cardiac problem, may not detect subtle
changes in exercise capacity until they are significant. By the
time the patients notice dyspnea and exercise limitation,
valvular residua and ventricular dysfunction are often severe
and irreversible.
All of these challenges emphasize the importance of impressing on patients, their families, and their physicians that all
cardiac surgery is palliative rather than curative and that
patients with congenital heart disease require lifelong
follow-up at centers where expertise is available to deal with
their complex problems. Two “simple” and two “complex”
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Adult Congenital Heart Disease
Abbreviations and Acronyms
ASD ⫽ atrial septal defect
AV
⫽ atrioventricular
BAV ⫽ bicuspid aortic valve
BP
⫽ blood pressure
eNOS ⫽ endothelial nitric oxide synthase
LV
⫽ left ventricle/ventricular
RV
⫽ right ventricle/ventricular
congenital cardiac anomalies that support this thesis will be
reviewed.
ATRIAL SEPTAL DEFECT (ASD)
Surgical repair of secundum ASD has been performed since
1954 and Murphy et al. (2) published the results of one of
the early pioneer series of symptomatic patients. They were
followed for 30 years, and patient survival was compared
with age-matched control subjects (Fig. 1). Although patients in the younger quartiles (⬍25 years) had normal
survival, patients ⬎25 years of age had a significantly
reduced survival compared with control subjects, and this
was even more striking in those ⬎40 years of age. Late
events, including atrial fibrillation, stroke, and heart failure
were more common in patients repaired in adulthood, and
this study was one of the first to demonstrate the benefits of
early repair of secundum ASD in symptomatic patients.
These residual problems after surgical repair in older patients have been confirmed in other studies (3–5). Presumably, this relates to the long-standing deleterious effects of
volume overload on the right-sided cardiac chambers, pulmonary hypertension, and right atrial enlargement that
increase the vulnerability to atrial arrhythmias and stroke. In
the series of Murphy et al. (2) 22% of late deaths were due
to stroke. Thus, although this common and simple cardiac
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anomaly can be easily repaired surgically and, in recent
years, closed percutaneously, it is not completely “cured” and
is associated with ongoing morbidity and mortality.
COARCTATION OF THE AORTA
Coarctation of the aorta is often regarded as a simple and
isolated congenital anomaly, but is more correctly interpreted as part of a diffuse arteriopathy with a propensity to
aneurysm formation and dissection remote from the coarctation site (6). In addition, more than 50% of patients have
an associated bicuspid aortic valve (BAV) and 10% of
patients have cerebral aneurysms demonstrated on magnetic
resonance image scanning of the brain, suggesting a common etiologic mechanism (7). After successful coarctation
repair, many patients consider themselves “cured,” and they
are often discharged from physician follow-up. It has long
been recognized that patients with repaired coarctation have
premature morbidity and even mortality (8,9). Late complications are common, and long-term survival may be far
from normal. A detailed knowledge of these complex
associations is critical in providing optimal care for these
patients.
The vulnerability of these patients to premature cardiovascular complications was exemplified in the largest series
ever reported after coarctation repair. Cohen et al. (8)
reported the long-term follow-up of 646 patients operated
on between 1946 and 1981. There were 17 perioperative
deaths, and 58 were lost to follow-up. Of 571 survivors, 67
patients had 81 subsequent cardiac operations, most frequently for aortic valve replacement or re-coarctation. There
were 87 late deaths, most commonly from acute myocardial
infarction and sudden cardiac death, and the 30-year survival of this cohort was 72%. The mean age at death for this
“simple” lesion was only 38 years. This emphasizes the
continued morbidity from premature coronary disease and
Figure 1. Long-term outcome of patients surviving the perioperative period according to age at operative closure of their atrial septal defect. Expected
survival in an age- and gender-matched control population is also shown. When patients undergo repair ⱖ25 years of age, survival is significantly reduced
compared with control subjects. Reprinted, with permission, from Murphy et al. (2).
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residual systemic hypertension, which is very common in
such patients.
Other late cardiovascular complications requiring subsequent surgery are common. In two series from the Mayo
Clinic (8,10), the most common reason for re-operation was
aortic valve replacement, but mitral valve repair or replacement in addition to re-operation for aortic aneurysm,
re-coarctation, and coronary artery bypass grafting are also
represented. All of these congenital arterial abnormalities
point toward a much more diffuse congenital cardiovascular
problem than might be suspected from a superficial review
of this “localized” narrowing in the aorta.
Residual hypertension and vascular reactivity. At 30year follow-up, as many as 75% of patients have residual
systemic hypertension (11). The pathophysiology of residual
hypertension in such patients is poorly understood, and it
occurs despite the absence of residual coarctation. Earlier
reports suggested that hypertension was less likely to occur
after early repair (12), but more recent reports suggest that
even after early repair, residual hemodynamic abnormalities
are common. O’Sullivan et al. (13) reported a 7- to 16-year
follow-up of 119 children having coarctation repair at the
age of 2 to 3 months. Of the patients, 28% had hypertension
at rest or during ambulation, including 21% who had no
residual aortic obstruction.
Even patients with normal blood pressure (BP) at rest
often demonstrate an abnormal systolic response to physical
exercise (14). This may contribute to increased left ventricular (LV) mass that has been reported even in normotensive
patients after repair, and which, in and of itself, is another
important predictor of cardiovascular complications (15).
Whether this increased LV mass is a genetically determined
hypertrophic response in coarctation or occurs because of
persistent hemodynamic or hormonal abnormalities remains
to be determined. Contributing causes may be changes in
the arterial pressure wave propagation in the aorta and/or an
increase in aortic stiffness or a “re-programming” of the
sympathetic nervous and/or renin-angiotensin system (14).
Vascular reactivity and mechanical properties of large
upper limb conduit arteries also continue to be impaired,
even in normotensive adults when successful coarctation
repair has been performed in the first few months of life
(16). Studies examining the brachial artery response to
flow-mediated dilation after reactive hyperemia (induced
either by inflation and deflation of a pneumatic cuff around
the forearm or administration of nitroglycerin) show less
dilation than in control subjects (14). Whether this represents early “programming” of vascular reactivity in utero or
an inherent arterial abnormality remains uncertain, but
clearly this might contribute to persistent cardiovascular
abnormalities such as increased LV mass and diastolic
dysfunction (17).
This impaired arterial response to increased flow suggests
an underlying endothelial dysfunction, and nitric oxide may
play a role in this regard and contribute to hypertension.
Nitric oxide is an important biological modulator that plays
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Adult Congenital Heart Disease
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Figure 2. Aortogram from a 40-year-old man with mild coarctation
(gradient 18 mm Hg). The entire aorta is dilated (ascending aorta ⫽ 40
mm), and the arch vessels are also dilated, indicating a diffuse arterial
problem.
a significant role in vasodilation and BP control. Studies in
animals have suggested a decreased nitric oxide bioavailability in the aortic segment proximal to the coarctation with
up-regulation of endothelial nitric oxide synthase (eNOS)
in this region. In contrast, distal to the coarctation, nitric
oxide activity is normal (18). This suggests a local baromechanical or endothelial etiology rather than a circulating
humoral factor that would be similar in both segments.
Diffuse arteriopathy. This “simple” focal lesion also posed
residual problems related to other areas of the arterial
system, which had a major impact on mortality and morbidity: stroke related to aneurysms of the Circle of Willis,
aortic aneurysm and dissection related to the inherently
abnormal aorta, and superimposed systemic hypertension
(Fig. 2). Ascending aortic aneurysm is the most frequently
encountered complication. Aortic complications resulting in
death or the need for surgery are frequent during adult life
in patients with repaired coarctation. The co-existence of a
BAV seems to influence their occurrence; in one series, the
prevalence of aortic complications was 22% (29 of 134
patients) in those with a BAV compared with 8% (8 of 101
patients) in those without a bicuspid valve (19).
BAV. Bicuspid aortic valve occurs in more than one-half of
the patients with coarctation and, therefore, periodic assessment of possible aortic valve disease is warranted even after
successful coarctation repair. Bicuspid aortic valve is also
one of the most common isolated congenital cardiac abnormalities, present in at least 1% of the population. Nitric
oxide may also play a role in this pathophysiology, because
mice lacking eNOS appear more likely to develop a BAV,
although the mechanism remains uncertain. It is possible
that valvular endothelium may generate signals that finetune the development of the primitive ventricular outflow
tract to ensure the development of a normal tricuspid
structure (20). Similarly, nitric oxide has been implicated in
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vascular remodeling in response to changes in luminal flow
conditions; so lack of eNOS might also affect the modeling
of the aortic isthmus during transition from the fetal to
adult pattern of circulation. Whether a deficiency of the
gene encoding eNOS exists remains unproven, but these
abnormalities of nitric oxide in both BAV and coarctation
are tantalizing and do implicate a unifying etiology. Further
research in this area is necessary.
Bicuspid aortic valve is also an independent risk factor for
progressive aortic dilation, aneurysm formation, and dissection. The aortic root dilation is unrelated to any hemodynamic disturbance of the valve itself, because ⬎50% of
young patients with a functionally normal aortic valve have
echocardiographic evidence of aortic dilation (21,22). This
diagnosis, too, should prompt the beginning of lifelong
surveillance of the arterial tree. Both coarctation and BAV
are part of a spectrum of arteriopathy, and the search for a
common pathophysiology is tantalizing. Two possible culprits include a genetic defect of fibrillin and/or an abnormality of nitric oxide metabolism.
Medial changes in the ascending aorta have been well
demonstrated and are identical to the changes seen with
coarctation. Histologic examination reveals smooth muscle
cell loss, fragmentation of elastic fibers, and “pools” of
basophilic ground substance in areas of cellular loss. The
exact cause of these degenerative changes in the aorta is
uncertain, but apoptosis may be an important underlying
mechanism causing the smooth muscle cell loss (23). There
may be an underlying genetic stimulus for programmed cell
death in the aortic media, and the recent observation that
BAV is heritable supports this concept (24).
Interestingly, de Sa et al. (25) reported that degenerative
changes in the media of the pulmonary artery are also more
common in patients with BAV, perhaps because the aorta
and pulmonary artery share the same embryologic origin
from the conotruncus. This would also support the concept
of a more diffuse “arteriopathy” and, perhaps, that BAV and
coarctation are part of a continuum of arterial abnormality.
Decreased levels of fibrillin-1 have also been reported in
the ascending aorta of patients with BAV, and this deficiency of fibrillin-1 may cause smooth muscle cells to detach
from the elastic laminae with the release of matrix metalloproteinases. These matrix metalloproteinases weaken the
aortic wall, degrade the fibrillin-1, and contribute to the
aortic dilation (26). Although the gene for fibrillin-1 may be
structurally normal in patients with BAV, it is possible that
transcriptional elements that control protein production
may be defective, thereby precipitating the arterial changes.
Follow-up. These important residua and sequelae support
the notion that patients with repaired coarctation need
lifelong follow-up with periodic imaging of the aortic valve
and the entire aorta. Two-dimensional echocardiography is
particularly helpful in this regard, and echo-Doppler assessment of the aorta facilitates measurement of the aorta,
coarctation site, and aortic valve. Magnetic resonance imaging provides a complementary adjunct to the evaluation
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and allows visualization of the entire aorta as well as
facilitating the detection of possible aneurysm formation at
the site of previous repair (usually not seen by echocardiography or chest radiograph). Histologic abnormalities of the
ascending aorta are common: the so-called “cystic medial
necrosis,” in which there is fragmentation of the elastic
fibers and accumulation of ground substance, making the
aorta vulnerable to aneurysm formation and dissection.
Blood pressure control should be meticulous to minimize
shear stresses on the aorta; this should be evaluated both at
rest and on exercise. Beta-blockade is ideal therapy in this
setting, although, as yet, there is no definite evidence that
they prevent aortic dilation as demonstrated in the Marfan
syndrome (27). Ambulatory BP monitoring may be helpful
if there is doubt about the effectiveness of BP control (13).
Careful attention should also be paid to BP at the time of
pregnancy, because hormonal changes exacerbate the distensibility of connective tissues, including those in the aorta,
and dissection and rupture of the aorta may occur during
pregnancy, especially around the time of delivery.
TETRALOGY OF FALLOT
Tetralogy of Fallot is one of the most common cyanotic
defects encountered in infancy. Lillehei et al. (28) performed the first repair in 1954, and operative results from
even the first 106 patients from the “pioneer era” were
excellent with a 30-year survival of 91%. The original repair
involved closure of the ventricular septal defect and resection of muscle from the infundibular region of the right
ventricular (RV) outflow tract (29). Because of the common
finding of a small annulus, however, subsequent repairs
often involved either a patch across the RV outflow or the
placement of a transannular patch. Although the patch is
effective in relieving the obstruction, it distorts the pulmonary valve apparatus and pulmonary regurgitation inevitably
results.
Pulmonary regurgitation. Pulmonary regurgitation is tolerated well for many years, even for decades, but the chronic
effects of long-term volume overload of pulmonary regurgitation eventually has a deleterious effect on RV function.
Exercise capacity declines, secondary tricuspid regurgitation
may occur, and supraventricular and ventricular arrhythmias
may supervene. Sudden death may be the presenting feature. Patients often do not notice symptoms until RV
dysfunction is severe. There is also a “ventricular-ventricular
interaction,” which occurs in the setting of RV enlargement
and systolic dysfunction, and concomitant LV dysfunction
is often observed (30). The mechanism that links RV
dysfunction to LV dysfunction, however, is incompletely
understood.
Pulmonary regurgitation is frequently overlooked on
physical examination, since the diastolic murmur is soft and
short because there is rapid equalization of the diastolic
pressures in the pulmonary artery and RV. The regurgitant
jet is also frequently missed on two-dimensional echocardio-
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graphy, because the jet has a low velocity and the flow is
laminar.
Any patient with previous surgical repair of tetralogy of
Fallot should have a normal heart size on chest radiograph,
and the observation of an increased cardio-thoracic ratio
should prompt a thorough search for a residual hemodynamic lesion. This may be a residual ventricular septal
defect, aortic regurgitation, or pulmonary stenosis. The
most common problem, however, is pulmonary regurgitation, and pulmonary valve replacement is the most common
indication for re-operation late after tetralogy repair (31).
Absence of symptoms does not reflect the functional derangement of the RV after tetralogy repair. Exercise testing
has demonstrated compromised exercise performance, and
hemodynamic data show elevated RV end diastolic volumes
along with reduced cardiac output and ejection fraction in
patients with pulmonary regurgitation (32,33).
Pulmonary valve replacement can be accomplished with a
low surgical risk (1% to 2%) in experienced centers, but
should be performed before there is irreversible RV dysfunction and the increased propensity for ventricular arrhythmias and sudden cardiac death (34,35). Timing of
pulmonary valve insertion is critical in reducing RV size,
preserving myocardial function, and preventing the development of arrhythmias (35). The precise indication for
pulmonary valve replacement remains uncertain, although
mounting evidence suggests that in many centers it has been
performed too late. Even when subjective improvement in
clinical symptoms is noted there is often no improvement in
either RV volumes or function (36). This must be balanced
against the concern of replacing the pulmonary valve early,
however, which means the patient faces another reoperation approximately 10 years later owing to structural
degeneration of the tissue prosthesis. Patients who require a
pulmonary valve replacement in the third or fourth decade
may require several re-operations in their lifetime.
Atrial and ventricular arrhythmias. Arrhythmias are also
common sequelae of repaired tetralogy. Atrial arrhythmias
may be present in approximately one-third of patients and
are a major source of morbidity (37). Although the prevalence of sustained ventricular tachycardia is low, it is
believed to be responsible for the small but definite incidence of sudden cardiac death in postoperative patients.
Pulmonary regurgitation is the predominant underlying
hemodynamic problem. Potential variables predictive of
death include older age at repair, heart failure, residual or
recurrent ventricular septal defect, and elevated RV pressure. Ventricular ectopy is common in this patient population, but neither frequent ectopy nor non-sustained ventricular tachycardia on ambulatory Holter monitor reliably
identifies patients at risk of ventricular tachycardia or
sudden death. Right bundle branch block is the expected
pattern on the electrocardiogram in 95% of patients, and a
“mechano-electrical” association has been demonstrated,
showing that the larger the RV size, the greater the trend
toward a longer electrocardiographic wave (QRS) duration.
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5
Mean QRS duration tends to be longer (⬎180 ms) in
populations of patients who die suddenly than in their
healthy counterparts (38). The rate of late progression of
QRS duration may also be a warning sign (39). Nonetheless, these findings, although having significance in large
populations of patients, have limited prognostic value in an
individual patient and have poor sensitivity and specificity.
The issue of whether electrophysiology studies are useful
to predict the development of clinical ventricular tachycardia has also not been resolved. Failure to induce ventricular
tachycardia may be interpreted as a favorable prognostic
sign, but a high proportion of patients have false-negative
studies despite aggressive stimulation protocols (40). It has
been suggested that the inclusion of polymorphic ventricular
tachycardia in the definition of inducibility improves the
sensitivity but with a slight reduction in specificity (41).
Furthermore, no study has conclusively demonstrated that
anti-arrhythmic medication improves survival. Thus, risk
stratification in postoperative patients after tetralogy repair
remains a major challenge, and the indications for implantation of a defibrillator device remain imprecise. Targeted
arrhythmia procedures at the time of pulmonary valve
replacement utilizing intraoperative electrophysiological
mapping and/or cryoablation appear to decrease the incidence of arrhythmias, at least in the short term (42).
Thus, since the time of the first surgical repair of tetralogy
of Fallot, the operation has been referred to as “total
correction.” This misnomer fosters the erroneous belief held
by patients that they are “cured” and that no further surgical
intervention will ever be necessary. This may prevent them
from seeking regular cardiac follow-up, so re-operation to
replace the pulmonary valve is often performed later than
ideal, when RV dysfunction is irreversible and patients are
vulnerable to arrhythmias and sudden cardiac death. Resentment is common when patients learn, to their dismay,
that another operation is necessary.
TRANSPOSITION OF THE GREAT ARTERIES
AND SYSTEMIC VENTRICULAR DYSFUNCTION
Simple transposition (d-transposition). Ventricular dysfunction is a common problem in many adults with congenital heart disease and is particularly common in those
born with transposition of the great arteries. Simple transposition (d-transposition) is the most common cyanotic
abnormality in newborns, in which the right atrium is
connected to the RV (atrioventricular [AV] concordance)
which, in turn, gives rise to the aorta (ventriculo-arterial
discordance). The left atrium enters the LV, which gives
rise to the pulmonary artery. Since the 1980s, this defect has
usually been repaired in infancy with an arterial switch
procedure so that the LV is restored to function as the
systemic ventricle. In the 1960s, however, the only reparative procedures were the Mustard or Senning operations
that redirect the blood flow via an atrial baffle so that venous
blood is directed into the LV and then to the pulmonary
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artery, and pulmonary venous blood is directed to the RV
and thence to the aorta. These operations resulted in a
dramatic improvement in the lives of cyanotic infants, who
were rendered pink and healthy, most of whom continue to
do well three decades later. Long-term problems are inevitable, however, particularly as the morphologic RV continues to function as the systemic ventricle This may function
well for decades (43), but function deteriorates eventually,
often with concomitant tricuspid regurgitation (44,45).
Pulmonary artery banding to “retrain” the LV followed by
an arterial switch operation has provided improvement in
systemic ventricular function in some young patients and
adolescents, but results of LV “conditioning” have been less
consistent in adults (46). As a result, this approach has been
largely abandoned in adults in favor of cardiac transplantation.
Congenitally corrected transposition (l-transposition). A
similar situation exists in those patients with congenitally
corrected transposition who have AV and ventriculo-arterial
discordance; congestive heart failure is common by the
fourth and fifth decades (47). In this situation, the morphologic RV is also the systemic pump, and the systemic AV
valve (the tricuspid valve) is frequently congenitally abnormal and vulnerable to regurgitation. The diagnosis of
congenitally corrected transposition may be missed by the
unwary physician who may overlook the abnormal position
and appearance of the ventricles on echocardiography and
fail to observe the more inferior tricuspid valve (closer to the
cardiac apex) on the left side. The tricuspid valve always
enters a morphologic RV, and the leaflets insert directly into
the ventricles rather than having attachments to papillary
muscles. In one study from the Mayo Clinic (48), the
diagnosis of congenitally corrected transposition had been
missed in 7 of 44 adults who had had a cardiology
consultation, despite the performance of one or more
imaging studies (echocardiography and/or cardiac catheterization). More importantly, most of these patients were
referred to a tertiary care center late for an evaluation. Of 30
patients who needed a systemic AV valve replacement for
severe systemic AV valve regurgitation, 16 had ⬎3/4 grade
AV valve regurgitation and had established systemic ventricular dysfunction for more than six months before referral. Even though AV valve replacement can be accomplished at a relatively low risk in experienced hands,
ventricular dysfunction has important prognostic implications. In one surgical series of 40 adult patients reported by
van Son et al. (49), the mean preoperative ejection fraction
was 48% (range 20% to 60%). There were four patients who
died perioperatively, and in a mean follow-up of 4.6 years,
eight patients subsequently died. The cause of death in all
12 patients was ventricular failure. Survivorship correlated
not only with more recent operations as surgical techniques
improved, but more importantly, with pre-operative ejection fraction (ejection fraction ⬎40%).
Follow-up. Therefore, it is imperative that patients with
congenitally corrected transposition have a detailed evaluation on a regular basis. This should include a physical
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Figure 3. (A) Chest radiograph of a 16-year-old young man with congenitally corrected transposition just after implantation of an endocardial
pacemaker. Reportedly, his systemic ventricular ejection fraction was 40%,
and he had moderate systemic atrioventricular valve (the tricuspid valve)
regurgitation. (B) Chest radiograph 18 months later at the time of referral.
His systemic ventricular ejection fraction was 15%, and he had severe
systemic atrioventricular valve regurgitation. Cardiac transplantation was
the only viable surgical option, because the referral was too late for
conventional operation.
examination, chest X-ray, electrocardiogram, and echocardiogram performed by someone with expertise in imaging
complex congenital anomalies. An increasing cardiothoracic
ratio or deterioration of systemic ventricular function should
prompt a careful search for systemic AV valve regurgitation.
Implantation of an endocardial pacemaker may also warrant
more frequent follow-up, because the change in septal activation causes septal “shift” and secondary dilatation of the
systemic AV annulus and subsequent regurgitation (Fig. 3).
Medical management. It is tempting to extrapolate the same
treatment strategies for those with ventricular dysfunction with
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acquired heart disease and those with congenital heart disease
and systemic (morphologic right) ventricular dysfunction. To
date, however, there is very little evidence that administration
of angiotensin-converting enzyme inhibitors or beta-blockers
has a beneficial effect on exercise capacity, ejection fraction, or
length of life in these patients (50). Indeed, some patients may
have abnormalities of ventricular filling related to abnormal
flow through the atrial baffle. Patients with postoperative
transposition and those with congenitally corrected transposition are particularly vulnerable to sinus node disease, and
injudicious use of beta-blockers may precipitate more profound
conduction disturbances and complete heart block. Multicenter trials are needed to determine the appropriate therapeutic modalities for patients with congenital heart disease and
systemic ventricular dysfunction when the RV functions as the
systemic ventricle.
7
CONCLUSIONS
Figure 5. Cardiac operations performed at the Adult Congenital Heart
Disease Clinic at Mayo Clinic from 1987 to 2003 (n ⫽ 1,284). More than
one-third of the patients had operation number 3 or higher. no. ⫽ number
of patients.
All of the lesions discussed exemplify the notion that babies
born with congenital heart disease are seldom “cured.”
Despite the phenomenal advances in diagnostic, medical,
and operative care that have occurred in the last 50 years,
many circulations still do not function normally, and residual problems are common. Cardiologists throughout the
U.S. still have little opportunity for exposure to adult
congenital heart disease, and despite training recommendations, few trainees have the opportunity to see such patients
during their fellowship. Many cardiologists, therefore, have
little understanding about the complexities of many postoperative residua and sequelae.
Patients often have a poor understanding of their anatomy and physiology and little concept of the possible
challenges the future may hold. The surgical descriptor
“total correction” fosters this misunderstanding, because
patients see little need to understand what was “fixed” and
no incentive to seek medical follow-up. Even when they do
seek follow-up, insurance obstacles often obstruct the path
to the few tertiary care centers where interdisciplinary
expertise and resources are available. All patients confront
many ongoing cardiac issues related to their congenital heart
disease, not to mention the impact that acquired hypertension, coronary artery disease, and other cardiovascular problems may impose on their underlying cardiac anomaly. This
becomes an increasing problem as the population ages (Fig.
4). In those who have had previous surgery, many face
multiple re-operations in their lifetime (Fig. 5), and each
subsequent operation poses an increasingly higher risk.
In conclusion, are these patients “born to be bad”? In
many ways, the answer is yes. They are seldom “cured” by
surgery and continue to have cardiac problems. Much time,
money, and effort has been devoted to secure their survival,
and unfortunately, very little thought has been given to
providing for their long-term care. These survivors are
extraordinarily courageous and usually, determined to work,
contribute to society, and be as normal as possible. In
adulthood, they often receive no care or suboptimal care,
perhaps the worst of any cardiovascular subspecialty. The
cardiology community serves them poorly, and, as we look
to the future, we must make provision for lifelong care by
trained physicians with expertise in their complex problems.
Reprint requests and correspondence: Dr. Carole A. Warnes,
Division of Cardiovascular Diseases, Mayo Clinic College of
Medicine, 200 First Street SW, Gonda 5-368, Rochester, Minnesota 55905. E-mail: [email protected].
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Figure 4. Age of the patient population seen at the Adult Congenital
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