Case 45
Aortopathy in Tetralogy of Fallot
Koichiro Niwa
Age: 37 years
Gender: Male
Occupation: Renal perfusionist
Working diagnosis: Tetralogy of Fallot
HISTORY
Soon after birth a murmur was heard and the patient had cya�
notic spells; the diagnosis of TOF was made. He did quite well
during childhood and adolescence. Later, at age 20, he under�
went repair, including closure of a VSD, resection of the RVOT
obstruction and pulmonary valvotomy. A transannular RVOT
patch was placed to relieve the obstruction. He recovered fully
and led a normal life. He completed his education and became
a medical engineer.
He was well until 1 year ago when he felt a rapid heartbeat
on some occasions and shortness of breath when climbing stairs.
His body weight gradually increased (10 kg over 6 months)
with pretibial pitting edema. He visited a local internist and was
prescribed diuretics. He was subsequently referred for further
evaluation.
He is a nonsmoker.
C o m m e n t s : In ACHD cases, the importance of obtaining
and reading the operative notes cannot be overemphasized.
Patients with repaired TOF without significant residua
(residual VSD or pulmonary stenosis) are usually well without
symptoms.
The patient has developed shortness of breath, palpitations,
and edema. Severe pulmonary regurgitation is not uncommon
after TOF repair and can be associated with RV dysfunction,
diminished exercise capacity, atrial and ventricular tachyar�
rhythmias (VTs) and sudden cardiac death. The VT usually
originates from the RVOT and can be fatal. Atrial flutter may
be observed in patients with tricuspid regurgitation. In some
cases, aortic regurgitation with aortic root dilatation may be
observed.
CURRENT SYMPTOMS
The patient could walk several blocks “on the flat” without dif�
ficulty but had shortness of breath and palpitations after climb�
ing one flight of stairs. He slept well lying flat without
dyspnea.
NYHA class: II
C o m m e n t s : His symptoms had become worse just over
the last several months, suggesting clinical deterioration.
CURRENT MEDICATIONS
Lasix 20 mg orally twice daily
Aldactone 25 mg orally twice daily
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Digoxin 250 µg orally once daily
Enalapril 5 mg orally twice daily
C o m m e n t s : ACE inhibitors are often used in patients
with aortic regurgitation to prevent progression, even though
there is no clinical trial evidence supporting this practice. Like�
wise, there are no data to support the use of ACE inhibitors or
any other agent in preventing the consequences of severe ���� pul�
monary regurgitation.
PHYSICAL EXAMINATION
BP 103/40 mm Hg, HR 89 bpm, oxygen saturation 98% in room
air
Height 182 cm, weight 72 kg, BSA 1.91 m2
Surgical scars: Median sternotomy scar
Neck veins: Normal A-waves, elevated V-waves were
observed
Lungs/chest: Chest was clear.
Heart: The first heart sound was normal. The second heart
sound was widely split. A grade 3/6 midsystolic murmur
was present at the third intercostal space near the left sternal
border. A grade 3/6 blowing early diastolic murmur was
present at the fourth intercostal space near the left sternal
border.
Abdomen: Moderate hepatomegaly
Extremities: Moderate dependent edema
Face: No facial features suggestive of velocardiofacial syndrome
(DiGeorge syndrome)
C o m m e n t s : The low diastolic blood pressure and wide
pulse pressure suggest there may be important aortic regurgi�
tation.
An elevated V-wave is indicative of tricuspid regurgitation.
A widely split second heart sound with a systolic and dia�
stolic murmur is commonly observed in patients with repaired
TOF. The delayed pulmonary component reflects delayed pul�
monary valve closure often due to a right bundle branch block.
The systolic murmur is typically due to residual pulmonary
stenosis (or RVOT turbulence due to a large stroke volume). A
diastolic murmur is often caused by pulmonary regurgitation,
though not always. In this instance, the high-pitched nature of
the diastolic murmur indicates that this is caused by aortic
regurgitation.
Cases in Adult Congenital Heart Disease  253
 There is a 10% to 15% incidence of chromosome 22q11 micro� tained VT and sudden cardiac death. In patients with prolonged
deletion in TOF patients, and those with the anomaly usually QRS, further examination such as an exercise ECG, late poten�
Right-Sided Lesions / Tetralogy of Fallot

show special facial appearance (velocardiofacial syndrome, or tials, and/or catheterization with electrophysiological study
DiGeorge syndrome; see Case 28). may be considered for refining the risk of VT and sudden
cardiac death.
LABORATORY DATA
CHEST X-RAY
Hemoglobin 14.9 g/dL (13.0–17.0)
Hematocrit 43% (41–51)
Sodium 140 mmol/L (134–145)
Potassium 4.0 mmol/L (3.5–5.2)
Creatinine 0.6 mg/dL (0.6–1.2)
Blood urea nitrogen 13 mg/dL (6–24)
BNP 167 pg/mL
ANP 170 pg/mL

C o m m e n t s : Brain natriuretic peptide (BNP) and atrial

natriuretic peptide (ANP) were grossly elevated in this patient,
compatible with cardiac failure and/or biventricular enlarge�
ment, though there is still much to be learned about the sig�
nificance of these markers in this patient population.
Other laboratory data were within normal limits.

ELECTROCARDIOGRAM
I aVR C1 C4

Figure 45-2  Posteroanterior projection.

II aVL C2 C5

Findings
Cardiothoracic ratio: 62%
III aVF C3 C6
The cardiac silhouette was grossly enlarged with calcification
in the RVOT. There was dilatation of the pulmonary arteries
II and ascending aorta. The RV and LV were also dilated.

C o m m e n t s : Patients with repaired TOF often have dila�

Figure 45-1  Electrocardiogram.
Findings
Heart rate: 89 bpm
PR interval: 200 msec
QRS axis: −100°
QRS duration: 110 msec
Sinus rhythm with RA overload (peaked P-waves in V2–3). T-
wave inversion in V1–4. Poor precordial R-wave progression.
No classical evidence of RV hypertrophy.
C o m m e n t s : While this case seems to be an exception,
after TOF repair an RBBB is nearly universal because of the
location of the bundle relative to the VSD. Left anterior hemi�
block and/or bifascicular block are also common. Bifascicular
block was once thought to be one of the predictors of complete
AV block and sudden cardiac death in patients with TOF repair.
However, this has not been confirmed in more recent studies.
Instead, monomorphic VT combined with RV dilatation and
pulmonary regurgitation is the major cause of sudden cardiac
death in TOF after repair.1 QRS prolongation over time suggests
RV conduction delay, which is related to both the risk of sus�
tation of the RV, main pulmonary artery, and right pulmonary
artery. RV dilatation is better seen on a lateral view. The left
pulmonary artery may be hypoplastic due to pulmonary branch
stenosis.
The ascending aorta in patients with TOF (even after repair)
may be enlarged due to increased systemic flow and cystic
medial necrosis in the aortic wall. Enlargement of the RA may
be associated with tricuspid regurgitation.
The arch is left-sided in this case. Right-sided aortic arch is
more commonly associated with enlargement of the aortic
root.1
EXERCISE TESTING
A cardiopulmonary test was not performed.
ECHOCARDIOGRAM
Overall Findings
The LVEDd was 56 mm. LV systolic function was normal. The
RV cavity was enlarged, and systolic function was decreased.
There was severe �����������������������������������������
pulmonary regurgitation������������������
and moderate tri�
cuspid regurgitation. The estimated RV pressure was 45 mm Hg.
The estimated pressure gradient across the RVOT was 35 mm Hg.

254  Cases in Adult Congenital Heart Disease

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 Ventricular Volume Quantification

Aortopathy in Tetralogy of Fallot

LV (Normal range) RV (Normal range)
EDV (mL) 195 (77–195) 255 (88–227)
ESV (mL) 95 (19–72) 130 (23–103)
SV (mL) 100 (51–133) 125 (52–138)
EF (%) 51 (57–75) 49 (50–76)
EDVi (mL/m2) 102 (66–101) 134 (65–111)
ESVi (mL/m2) 50 (18–39) 68 (18–47)
SVi (mL/m2) 80 (43–67) 55 (39–71)

Findings
The ascending aorta measured 51 mm in diameter.

C o m m e n t s : MRI is a very useful imaging modality for

Figure 45-3  Parasternal long-axis view, 2D color Doppler.
Findings
Echocardiography revealed no residual VSD. There was ascend�
ing aortic root dilatation (root diameter of 46 mm) with moder�
ate aortic regurgitation.
C o m m e n t s : Measurement of RV/LV size and assessment
of RV/LV function by echo and change over time may be the
best guide to optimal timing of intervention. This patient was
diagnosed as having biventricular volume overload and RV
dysfunction due to a combination of pulmonary regurgitation
and aortic regurgitation with a dilated aortic root.
In our opinion, moderate aortic regurgitation with a dilated
aorta and/or RV failure together with pulmonary regurgitation
warrants consideration of surgery with aortic valve replace�
ment and/or aortic repair. The leaflets themselves appear
normal, and therefore the cause of regurgitation is most likely
the dilated root.
assessing RV function, pulmonary
�������������������������������������
regurgitation��������������
and/or steno�
sis, as well as aortic root dilatation. When these lesions coexist,
it is necessary to use phase contrast velocity mapping to quan�
tify regurgitant flow, rather than compare the stroke volumes.
The presence of tricuspid regurgitation also increases the RV
stroke volume.
This MRI confirmed the presence of not only RV dilatation
with severe pulmonary regurgitation (see Case 41) but also a
dilated ascending aorta with moderate aortic regurgitation.
Risk factors for aortic root dilatation in repaired TOF are older
age at repair, male sex, longer interval after placement of a pal�
liative shunt, and right aortic arch.1

MAGNETIC RESONANCE IMAGING

Overall Findings
Both ventricles were dilated. The function of the RV was mildly
impaired, as was the LV. The left aortic arch and dilated A
ascending aorta were abscribed in the systolic phase. No resid�
ual VSD was seen.
The study also showed moderate tricuspid regurgitation and
trivial mitral regurgitation. In the four-chamber view, the RA
was moderately dilated. By phase-contrast velocity flow
mapping, the regurgitant fraction of the pulmonary valve was
55%, and of the aortic valve was 52%.

Figure 45-5  Transaxial plane, spin echo imaging. Great vessels level, in
end-systolic phase (A) and end-diastolic plase (B).

Findings
There was a dilated ascending aorta and a dilated main pulmo�
nary artery.

C o m m e n t s : Measurement of the aorta will vary depend�

ing on both the level and the imaging plane used to measure.
When serial measurements are performed, they should be
Figure 45-4  Coronal plane spin echo (black blood) imaging. done at the same level in the same plane. The coronal plane is

Cases in Adult Congenital Heart Disease  255

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 convenient because the curvature of the aorta is easily seen genital heart defects. These include bicuspid aortic valve and/or
and can be accounted for. However, the entire aorta is not coarctation, single ventricle, truncus arteriosus, and transposition
Right-Sided Lesions / Tetralogy of Fallot

visible (e.g., the aortic root is not seen in this particular of the great arteries, as well as TOF.
plane). The axial images are routinely acquired, and the pulmo�
2. What is the cause of aortic root dilatation and aortic
nary artery bifurcation is a convenient landmark on which to
regurgitation?
reference serial measurements.
There are two possible reasons for the aortic dilatation seen in
TOF and other congenital abnormalities. One is high flow through
CATHETERIZATION (PREOPERATIVE) the aorta, as seen in pulmonary atresia or with palliative aorto-
pulmonary shunts. The second is a histological abnormality of
Hemodynamics the tunica media, incorrectly called “cystic medial necrosis,”
Heart rate 85 bpm leading to gradual weakening of the muscular wall. The process
is particularly well recognized in Marfan syndrome, annuloaor-
Pressure Saturation (%) tic ectasia or Turner syndrome, as well as conditions such as
SVC mean 12 68 systemic hypertension, pregnancy, and normal aging. The cause-
IVC mean 11 71 effect relationship between cystic medial necrosis and aortopa-
RA mean 12 thy, however, requires further study.
RV 50/10 Usually, there is no abnormality of the aortic valve leaflets
PA 28/10 mean 17 69 themselves, unless there has been some iatrogenic damage at the
PCWP mean 12 time of repair or postendocarditis. Aortic root dilatation may
LV 108/11 eventually lead to aortic regurgitation. There are rare cases of
Aorta 113/39 mean 69 98 aortic dissection in patients with previous tetralogy repair (and
Gradient (pullback) from PA to RV: 28 mm Hg aortic root dilatation), albeit in patients with additional risk
factors (such as systemic hypertension).
Calculations
Qp (L/min) 4.23 3. Should this patient undergo surgical repair of the aortic
root and/or replacement of the aortic valve?
Qs (L/min) 4.19
Cardiac index (L/min/m2) 2.20 Mild aortic regurgitation is reported in 15% to 18% of patients
Qp/Qs 1.01 with repaired TOF, and aortic valve or aortic root replacement is
PVR (Wood units) 1.42 required in a small percentage of these patients.
SVR (Wood units) 13.60 It would seem prudent that decisions about the need for and
timing of aortic root surgery are made similarly to decisions con-
Findings cerning other forms of acquired aortic root/valve disease. Hence,
Residual pulmonary stenosis was present, but this was mild. the size of the aortic root, the degree of aortic insufficiency, the
Cardiac output was decreased. size and function of the LV, and so forth, are all important.
This approach, however, is somewhat controversial, and not
C o m m e n t s : The low cardiac index is concerning. The all centers would view root enlargement after repair of TOF in
stroke volume of both ventricles is high, as calculated by MRI, the same way. Reports of rupture of the ascending aorta in
but the relatively low mixed venous saturations indicate that conotruncal abnormalities are exceptionally rare at present,
oxygen tissue delivery is compromised. The wide pulse pres� hence the speculation that the natural history of aortic dilatation
sure is consistent with significant aortic regurgitation. in these patients may be different. It is also possible that, because
root dilatation seems to be related to the timing of initial repair,
Angiography this late complication may be less common as infants with tetral-
Not performed ogy are repaired earlier in life. However, this is speculative, and
vigilance on the aortic root size is warranted both for the older
patients and for more contemporary cohorts of tetralogy undergo-
Focused Clinical Questions ing earlier repair.
and Discussion Points In our opinion, this patient has moderate aortic regurgitation
with an enlarged, mildly dysfunctional LV and low cardiac
output with concomitant significant pulmonary regurgitation;
1. Is aortic dilatation an unexpected finding in this patient?
thus elective aortic surgery at the time of pulmonary valve
The finding of aortic root dilatation is not surprising. Although implantation was recommended. It may be possible to spare the
TOF is considered mainly a lesion involving the RV and pulmo- aortic valve after repairing the dilated root.
nary valve, aortic root dilatation is a well-recognized feature.
4. Should the patient have surgery for his pulmonary regur-
Aortic root dilatation, defined as a ratio of observed/expected
gitation?
aortic root size by standard nomogram greater than 1.5, was found
in 15% of adults with TOF late after repair.2 Factors associated The decision to replace the pulmonary valve after repair of
with this finding included male gender, pulmonary atresia, right TOF is a common dilemma, and factors to consider in making
aortic arch, a longer shunt-to-repair interval, moderate to severe such a decision are discussed elsewhere (see Case 41). Here, our
aortic regurgitation, aortic valve replacement, a larger cardiotho- patient has severe pulmonary regurgitation; and established RV
racic ratio, and increased left ventricular end-diastolic dimen- dysfunction and symptoms, so that all criteria for pulmonary
sions. The association of chromosome 22q11 deletion (DiGeorge valve implantation are met.
syndrome, see Case 28) has also been proposed to be a risk factor
for aortic root dilatation. FINAL DIAGNOSIS
Although the aortic root and the ascending aorta are often
dilated in patients after tetralogy repair, aortic regurgitation is TOF (repaired), moderate to severe pulmonary regurgitation
seldom more than moderate.3,4 with RV dysfunction
The ascending aorta may often dilate out of proportion to
hemodynamic or morphogenetic expectations in a variety of con- Moderate aortic regurgitation, aortic root dilatation

256  Cases in Adult Congenital Heart Disease

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PLAN OF ACTION
Surgical aortic valve/root replacement and implantation of a
stented porcine valve in the pulmonary position
INTERVENTION
The ascending aorta was dilated to 50 mm. The wall of the
ascending aorta was fairly thick. The aortic cusps were slightly
thickened and elongated. Aortic valve replacement with a 25-
mm St. Jude Medical device was performed. The RV was also
dilated. The original pulmonary valve was thickened and
bicuspid. A stented porcine valve was implanted in the area of
the pulmonary annulus with concomitant reconstruction of the
RVOT.
OUTCOME
The postsurgical course was uncomplicated, and the patient
made a complete recovery. He was maintained on furosemide,
beta-blockers, and warfarin.
Catheterization was performed 1 year after reintervention, as
is our unit’s policy. There was no residual gradient between the
RV and PA, nor was there any residual ��������������������
pulmonary regurgita�
tion or aortic regurgitation. Angiographic volumes suggested
reduction in RV and LV size with preserved systolic function.
The cardiac index had improved.
A VT stimulation electrophysiological protocol at the time
was negative.
Diuretics were discontinued at that point in time, but he
was advised to continue with warfarin and beta-blockers
indefinitely.
The patient’s exercise capacity was subjectively better 2 years
after his operation, and the patient remained arrhythmia free
and asymptomatic.
Selected References
1. Gatzoulis MA, Till JA, Sommerville J, et al: Mechanoelectrical
interaction in tetralogy of Fallot. QRS prolongation relates to right
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For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
ventricular size and predicts malignant ventricular arrhythmias
and sudden death. Circulation 92:231–237, 1995.
Aortopathy in Tetralogy of Fallot
2. Niwa K, Siu S, Webb G, et al: Progressive aortic root dilatation in
adults late after repair of tetralogy of Fallot. Circulation 106:
1374–1378, 2002.
3. Capelli H, Ross D, Somerville J: Aortic regurgitation in tetrad of
Fallot and pulmonary atresia. Am J Cardiol 49:1979–1983, 1982.
4. Dodds GA, III, Warnes CA, Danielson GK: Aortic valve replace-
ment after repair of pulmonary atresia and ventricular septal defect
or tetralogy of Fallot. J Thorac Cardiovasc Surg 113:736–741, 1997.
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Cases in Adult Congenital Heart Disease  257