PRIMER

Management of Systemic Right Ventricular

Failure in Patients With Congenitally Corrected
Transposition of the Great Arteries

ABSTRACT: In recent decades, significant progress has been made in Aleksei A. Filippov, MD
the diagnosis and management of congenitally corrected transposition Pedro J. del Nido, MD
of the great arteries (ccTGA). Nevertheless, gradual dysfunction and Nikolay V. Vasilyev, MD
failure of the right ventricle (RV) in the systemic circulation remain the
main contributors to mortality and disability for patients with ccTGA,

STATE OF THE ART

especially after adolescence. Anatomic repair of ccTGA effectively
resolves the problem of failure of the systemic RV and has good early and
midterm results. However, this strategy is applicable primarily in infants
and children up to their teens and has associated risks and limitations,
and new challenges can arise in the late postoperative period. Patients
with ccTGA manifesting progressive systemic RV dysfunction beyond
adolescence represent the major challenge. Several palliative options
such as cardiac resynchronization therapy, tricuspid valve repair or
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replacement, pulmonary artery banding, and implantation of an assist

device into the systemic RV can be used to improve functional status and
to delay the progression of ventricular dysfunction in patients who are not
suitable for anatomic correction of ccTGA. For adult patients with severe
systemic RV failure, heart transplantation currently remains the only long-
term lifesaving procedure, although donor organ availability remains one
of the most limiting factors in this type of therapy. This review focuses on
current surgical and medical strategies and interventional options for the
prevention and management of systemic RV failure in adults and children
with ccTGA.

Correspondence to: Nikolay
V. Vasilyev, MD, Department of
Cardiac Surgery, Boston Children’s
Hospital, Harvard Medical School,
300 Longwood Avenue, Boston,
MA 02115. E-mail nikolay.
vasilyev@childrens.harvard.edu
Key Words: congenitally
corrected transposition of the
great arteries ◼ heart diseases
◼ heart failure ◼ surgery

© 2016 American Heart

Association, Inc.

Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106 October 25, 2016 1293

 Filippov et al
C
ongenitally corrected transposition of the great ar-
teries (ccTGA) is a rare but well-described congeni-
tal cardiac malformation with an incidence of ≈1
in 33 000 live births (0.5% of all patients with congeni-
tal heart defects). Morphologically, ccTGA comprises a
combination of atrioventricular and ventricular-arterial
discordance (“double discordance”).1 In up to 80% of
cases, ccTGA is accompanied by associated cardiac le-
sions: ventricular septal defects (VSDs) in 60% to 80% of
cases, pulmonary stenosis in ≈50%, and abnormalities
of the conduction system in 15% to 50%.1
Patients with isolated ccTGA usually are asymptom-
atic early in life and can survive well into adulthood.
However, in this scenario, the right ventricle (RV) and
the tricuspid valve (TV) support systemic circulation for
decades, which can lead to gradual dysfunction and fail-
ure of these structures. Therapeutic options for adult
patients presenting with failing systemic RV are quite
limited, and the number of these individuals will increase
during the next decades,2,3 making the development of
an effective strategy for the management of these pa-
tients one of the more important unresolved problems.
RV in the Systemic Circulation
In ccTGA, the RV presents as a systemic pumping
chamber; therefore, its structural and morphological
relationships and the interventricular interactions be-
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come abnormal. High systolic pressures inside the RV
lead to eccentric hypertrophy of its free wall, shift of
the interventricular septum toward the left ventricle (LV),
and dilation of the RV, resulting in increased ventricular
wall stress and dysfunction of the trabecular component,
papillary muscles, and valvar apparatus of the RV.4
Coronary Arteries
The coronary arteries in ccTGA are inverted, arise from
anterior and posterior aortic sinuses, and follow their
respective ventricles. The systemic RV is supplied only
by the left-sided (morphologically right) coronary artery,
which can lead to inadequate perfusion of the hypertro-
phied ventricular mass and deterioration of the RV func-
tion with increasing age. Despite the significant increase
in myocardial blood flow through the right coronary ar-
tery, hypertrophy of the RV is not supported by adequate
proliferative response of the capillary vasculature. Coro-
nary flow reserve is significantly decreased in patients
with ccTGA even in the absence of ischemic symptoms,
and global RV dysfunction is strongly correlated with at-
tenuated maximal coronary blood flow.5,6 Radionuclide
scanning indicated myocardial perfusion defects corre-
lated with regional thickening and abnormal motion of
the ventricular wall in adult and pediatric patients with
ccTGA at the subclinical stage.7 It is interesting to note
that a more recent study did not find myocardial fibro-
1294 October 25, 2016
sis of the RV resulting from recurrent ischemia as a sig-
nificant contributor to systemic RV failure, although the
sensitivity of the imaging technique used may not allow
detection of microscopic fibrosis.8 Nevertheless, relative
coronary insufficiency can play an important role in the
development of late RV dysfunction and asymptomatic
ischemia in older patients with ccTGA after the fourth
decade of life.
Conduction System
The conduction system in ccTGA is distinctly abnormal
because of the malalignment of the atrioventricular sep-
tum. The conduction system takes a longer course to
the ventricles, which can be a reason for the occurrence
of ventricular arrhythmias and complete heart block, es-
pecially with increasing age.6 Dilation of the atrial cham-
bers and abnormal shift of the atrioventricular septum
over time are also given to be reasons for emergence of
supraventricular arrhythmias and heart block in patients
with ccTGA.9,10
TV in the Systemic Circulation
Tricuspid regurgitation (TR) has been found to be a
major contributor to the development of progressive
RV dysfunction and failure in adult patients with ccTGA
with a systemic RV.4,11,12 In ccTGA, RV hypertrophy is
followed by dilation, and the ventricular shape becomes
more spherical. The tricuspid annulus dilates; papillary
muscles move away from the inflow tract; and tethered
cords do not allow the leaflets to occlude the orifice.
These mechanisms predispose to the steady increase
in TR over time.
Some patients with ccTGA have coexistent lesions of
the TV. The most common one is an Ebstein-like thicken-
ing and shortening of the cords and, in some patients,
apical displacement of the septal and mural leaflets.1,11
This group of patients is more likely to develop signifi-
cant TR and ventricular dysfunction early in life.2
Associated Intracardiac Lesions
A VSD and obstruction of the pulmonary valve are most
commonly associated with ccTGA. The VSD is usually lo-
cated beneath the pulmonary valve in the conoventricular
region. Patients with large VSDs present with left-to-right
shunt resulting in pulmonary overflow early in infancy.
Obstruction of the pulmonary outflow tract occurs in
≈50% of cases. In ccTGA, the pulmonary artery (PA) is
positioned deep inside the crux of the heart, between
the mitral valve and TV, and this location predisposes
it to subvalvar obstruction. The pulmonary outflow tract
can be obstructed by accessory fibrous tissue from
the septum and mitral valve or by the accessory tissue
around the VSD.1
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106

Clinical Presentation and Assessment
of Systemic RV Function
Clinical symptoms in infancy and early childhood depend
on the presence and severity of associated intracardiac
lesions. Complete heart block occurs in 10% to 15% of
patients at birth, and its incidence increases over time,
reaching >30% in adult patients.
Patients without significant associated intracardiac
lesions usually do not have symptoms of heart failure
in childhood and do well until adult life. However, the
RV dysfunction progresses over time, as does TR. RV
dysfunction usually remains subclinical for decades and
typically manifests during fourth and fifth decades of
life.1 By 45 years of age, >30% of patients with isolated
ccTGA and more than two thirds of patients with asso-
ciated lesions develop clinical congestive heart failure.
The mortality among 77 adult patients with ccTGA was
reported by Dobson et al12 as 16% at 40 years of age,
and most deaths were caused by atrial tachyarrhythmia,
sudden death, or congestive heart failure.
Adult patients with systemic RV can develop severe RV
failure or fatal tachyarrhythmia unpredictably. Therefore,
these patients require regular (every 6–8 months) follow-
up, including echocardiography and a treadmill exercise
test. Systemic RV dysfunction can be identified at the
subclinical stage if sensitive measures of myocardial per-
formance are used.12,13 Cardiac magnetic resonance and
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routine echocardiography imaging are useful in identify-
ing subclinical RV dysfunction, especially if quantitative
parameters (RV index of myocardial performance, tissue
displacement, and strain) are calculated. The degree
of TR might be underestimated by echocardiography in
some patients; therefore, cardiac magnetic resonance
should be used in patients with progressive TR to decide
whether surgical intervention on the TV is necessary. Pa-
tients with systemic RV and a history of cardiac surgery
in infancy have higher risk of adverse outcome (sudden
death, RV failure, TR) and require special attention.
Surgical Management of the Failing
Systemic RV in Patients With ccTGA
Surgical management of ccTGA implies 2 basic strate-
gies. The strategy of physiological repair was introduced
in the early 1960s. It involves repair of associated car-
diac anomalies and surgical palliations to improve the
patient’s clinical presentation and prognosis. The RV
remains the systemic pumping chamber in physiologi-
cal repair. This strategy was widely used during 3 de-
cades, but long-term follow-up demonstrated suboptimal
outcomes in these patients. In the 1990s, physiological
repair was replaced by a strategy of anatomic correc-
tion in most centers. However, many patients remain
with a systemic RV with isolated ccTGA or with physi-
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106
Management of Systemic RV Failure in ccTGA
ological repair only. The management options for those
who present with RV dysfunction and failure are limited.
Assessment should be made if they are candidates for
anatomic repair or remain with a systemic RV, but as-
sociated lesions such as TR, complete heart block, or
clinically important VSDs with associated pulmonary ste-
nosis can be treated.
Anatomic Repair: Single Versus Staged
In selected cases in which the ventricular dysfunction
is confined to the RV and the LV has preserved systolic
function, an anatomic repair can be considered. Except
in cases in which the LV is at systemic pressures such
as patients with a large VSD and pulmonary stenosis, an
anatomic repair usually requires staged LV preparation to
gain muscle mass before it can support the systemic cir-
culation. In the former case in which the LV is at systemic
pressures as a result of the VSD and pulmonary stenosis,
proceeding directly to an anatomic repair with a Mustard/
STATE OF THE ART
Senning atrium-level switch plus a Rastelli-type LV to aor-
tic tunnel and RV to PA conduit offers the best long-term
option.3,14,15 Unfortunately, these cases are rare.
More commonly, the LV requires preparation with a
PA band to increase afterload in an effort to induce ven-
tricular hypertrophy. This strategy is most successful
early in life when somatic growth is still high. In older
teens and adults, the ability of the LV to increase muscle
mass without inducing fibrosis is very limited. Success-
ful preparation of the LV is possible only in young infants
and children <15 years of age,3 with rare exceptions.
In a small number of adult patients who have high
(close to systemic) LV pressures caused by coexistent
nonrestrictive VSD or significant pulmonary stenosis,
staged anatomic correction at a later age may be pos-
sible (Figure 1). Cardiac magnetic resonance measure-
ment of muscle mass and indexes of systolic function
is very important, along with cardiac catheterization to
measure end-diastolic pressure, before anatomic correc-
tion is considered in these patients.
PA Banding as a Palliative Procedure
The PA banding procedure in ccTGA can have 2 aims:
preparation of the LV for anatomic repair and as a pal-
liative procedure aimed at improving RV function by
reducing TR and restoring normal geometric relation-
ships between the RV, interventricular septum, TV, and
subvalvar structures. The mechanism of PA banding in
ccTGA with RV and TV dysfunction is thought be due
to the fact that the PA band elevates the LV pressure,
reduces leftward septal shift, prevents further tricus-
pid annular dilation, and therefore improves the stage
of heart failure.4 Some patients have significantly im-
proved ventricular function with banding alone, and this
October 25, 2016 1295
 Filippov et al

Figure 1. Management of pediatric patients with congenitally corrected transposition of the great arteries
(ccTGA) with systemic right ventricle (RV).
LV indicates left ventricle; PA, pulmonary artery; and VSD, ventricular septal defect.

approach can be used for prophylaxis and manage- tion after banding. Early PA banding also resulted in fa-
ment of RV failure in patients with isolated ccTGA or as vorable function of the neoaortic valve after anatomic
a palliative surgery in patients not suitable for anatomic correction. Older children and adolescents respond to
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correction.16 Good intermediate results of this “open-
ended” palliation in 15 pediatric patients with ccTGA
were reported by the group from Leuven.17
A recent clinical trial from our institution18 reported
results of PA banding for LV preparation in 25 pediatric
patients, 18 of whom subsequently underwent anatomic
repair. All 12 patients who were banded before 2 years
of age had improved morphological RV function and were
free of LV failure after PA banding, and 11 of them un-
derwent anatomic repair and had preserved biventricular
function. In comparison, 4 of 6 patients with PA banding
performed after 2 years of age developed LV dysfunc-
PA banding by hypertrophy rather than hyperplasia; as a
consequence, they may be more likely to develop rapid
LV diastolic dysfunction. Impaired contraction and relax-
ation of the LV as a result of hypertrophy significantly
compromise outcomes in this group, especially if pa-
tients are banded for a long period.16
Results of Anatomic Correction
A summary of the largest trials on midterm results of
anatomic repair is presented in the Table. Early and
midterm outcomes of particular surgical techniques are

Table.  Early and Intermediate Results for Anatomic Correction of ccTGA

Double- Freedom From
Switch/Senning- Median Mean Postoperative Reintervention/
Author(s) and Year of Patients, Rastelli Group, n (Range) Age Follow- Midterm Left Ventricular Heart
Publication n patients at Surgery, y Up, y Survival, % Dysfunction, % Transplantation, %
Bautista-Hernandez et 1.6
44 21/23 3.0 … 18 73
al,19 2006 (0.6–39.6)
Gaies et al,20 2009 65 35/30 2.5/1.9 5.8/3.2 77 N/A 75/98.5
Hiramatsu et al,21 2012 90 18/72 7.4/4.3 12.9/10.9 81 15 81/100
Langley et al, 2003
22
51 29/22 3.2 (0.14–40) 4.4 89.7 12 77.5
Hraška et al, 2011
23
2
23 9/13 3.4 100 0 77/ 100
(0.3–15.7)
ccTGA indicates congenitally corrected transposition of the great arteries.

1296 October 25, 2016 Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106


dependent on the complexity of cardiac anatomy and
conduction system, presence and hemodynamic sig-
nificance of associated intracardiac lesions, severity of
heart failure, and conditions of the LV before surgery. In
most centers, anatomic repair became the surgery of
choice for management of ccTGA in the early 1990s.
Therefore, large, multicenter, clinical trials describing
long-term outcomes have not been published yet. How-
ever, results of a few studies with a median follow-up of
5 to 12 years are available.21,24–26 According to these
data, several important factors have a major influence
on long-term outcomes: late LV dysfunction and failure,
occurrence of complete or high-degree heart block and
pacemaker implantation, neoaortic valve regurgitation,
obstruction of Senning/Mustard pathways, and the need
for regular reinterventions if conduits have been used.26
However, TV function significantly improves after ana-
tomic repair, and direct surgical intervention on the TV is
usually not necessary.27
All investigators confirmed satisfactory late results
of double-switch procedures. Survival at 10 to 20
years after surgery was reported as 75% to 85% in the
largest series,21,25 and freedom from any reinterven-
tion varied between 49% and 95%, mostly because of
the need for conduit change. Functional outcomes of
anatomic repair are also reported as good; >86% of
survivors are at New York Heart Association functional
class I or II.21,23,25 In addition, anatomic repair has su-
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perior results in higher-risk groups (ie, patients with
significant TR) compared with physiological repair.24
Results of the initial studies describing long-term out-
comes of the anatomic repair are encouraging, but
late morbidity is significant, and well-designed, large,
multicenter, clinical trials and meta-analyses are nec-
essary to address all the complex issues and to sup-
port this strategy.
Palliative Procedures With Systemic RV
The strategy of physiological repair includes several
surgical approaches to restore normal physiology but
does not correct the main anatomic abnormality, the
combination of discordant atrioventricular and ventricu-
lo-arterial connections, which leaves the RV as the sys-
temic ventricle. Until the last decade of 20th century,
preference was given to this strategy. More recently,
anatomic repair has been most commonly applied de-
spite its technical challenges and a wide list of potential
contraindications and limitations, the most important of
which is the need for a prepared LV. However, elements
of physiological repair that treat associated anomalies
can be performed in adult and adolescent patients with
complex anatomy and therefore remain a valuable op-
tion for the management of patients with ccTGA with
systemic RVs in the current era.
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106
Management of Systemic RV Failure in ccTGA
Correction of Associated Cardiac Anomalies
The repair of associated cardiac anomalies in physiologi-
cal repair (maintaining systemic RV) comprises closure
of the VSD, repair or replacement of the TV (if neces-
sary), and surgical palliations aimed at avoiding mor-
phological LV decompression and septal shift into the
LV such as PA banding. Elements of physiological repair
can be used in symptomatic children, postpubescent
patients, and adult patients with significant associated
lesions, but >50% of these patients require delayed sur-
gery or intervention during follow-up.24
TV Surgery
TV surgery may be a good option for patients with pro-
gressively worsening TR and relatively well-preserved
ventricular function. TR leads to volume overload of the
systemic RV and exacerbates systemic RV dysfunction.
Timely surgical intervention on the TV can interrupt this
process and thus improve long-term outcomes. How-
STATE OF THE ART
ever, TV repair in patients with systemic RV is techni-
cally difficult and has suboptimal midterm and long-term
results with a high rate of recurrent TR.28 Exposure to
the systemic TV can be challenging, depending on the
position of the apex of the heart. The more midline the
ventricular mass is, the more rotated the TV is and the
harder it is to access the entire valve. In situs inversus
(I,D,D), this can be even more challenging. Extensive
mobilization of the pericardium and opening the pleu-
ral space to allow rotation of the heart can be a useful
technique for exposing the valve. In most cases, with
the exception of young infants, an annuloplasty ring is
required to achieve a more durable repair. Mobilization of
a tethered septal and anterior leaflet, particularly at the
anteroseptal commissure, is often required in cases in
which the septal leaflet is apically displaced or tethered.
TV replacement results in immediate improvement of
TV function and can delay or prevent the development
of heart failure in adult patients with ccTGA. However,
early and late mortality after TV replacement is substan-
tial.29 Moreover, valve replacement can be performed
mainly after adolescence, when the tricuspid annulus
has reached adult size and the patient will not outgrow
the prosthesis. Despite the fact that the regurgitation is
eliminated, patients with TV replacement have the worst
outcome among patients with ccTGA because of pro-
gressive heart failure.30 RV function has a great influence
on the outcome of this procedure. In a trial from the
Mayo Clinic, preoperative RV ejection fraction <40% and
morphological LV systolic pressure >50 mm Hg (caused
by significant pulmonary outflow tract obstruction or pul-
monary hypertension) were identified as the most sig-
nificant predictors of late RV failure, mortality, or need
for cardiac transplantation after TV replacement.31 It is
important to note that successful TV repair or replace-
ment prevents the progression of RV dysfunction in most
October 25, 2016 1297
 Filippov et al
patients and improves New York Heart Association func-
tional class, but in most cases, it may not improve pre-
existent RV failure significantly.11 Therefore, this type of
surgery should be performed early to preserve the sys-
temic RV function. Permanent and significant progres-
sion of TR is a key indication for TV repair or replace-
ment, even if the regurgitation itself does not seem to be
severe at the time of surgery. Patients with atrial fibrilla-
tion and pulmonary outflow tract obstruction resulting in
high pressures in the morphological LV should be closely
assessed before surgery, and simultaneous procedures
may be performed to achieve favorable results.
Alternative and Prospective Options in
Management of Severe RV Dysfunction
After Adolescence
Adult patients with systemic RV in biventricular circula-
tion and objective signs of even mild but progressing
RV dysfunction or TR have a poor long-term prognosis.
Stage of heart failure, degree of TR, and incidence of
life-treating arrhythmias inevitably increase in these pa-
tients. Heart transplantation is the only radical lifesaving
option for adult patients with ccTGA with advanced sys-
temic RV dysfunction. However, this option is not always
available for patients with ccTGA. Even if the patient is
listed for heart transplantation, survival until donor heart
availability requires careful medical management and of-
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ten interim interventions. Therefore, several alternative
palliative surgical options have been used to delay the
progression of heart failure, to improve the functional
status of these patients, or to provide bridge to trans-
plantation (Figure 2).
High-Degree Heart Block and Pacer Choice
If advanced second- or third-degree atrioventricular
block is present, pacemaker implantation may be nec-
essary. However, late-onset systemic ventricular dys-
function is the most common complication after pacer
insertion. A recent trial from our institution described
intermediate (median follow-up, 3.7 years) results af-
ter pacemaker implantation in 53 pediatric and adult
patients with ccTGA.32 Thirteen pacemaker recipients
(26%) had systemic RVs: 9 patients underwent pacer in-
sertion at the time of preparing for anatomic repair, and
4 patients with systemic RVs developed spontaneous
heart block. Univentricular pacing was performed in 42
patients, and 22 of them developed significant late-onset
systemic ventricular failure. Subsequently, 17 of these
patients were upgraded to a biventricular system in an
effort to achieve resynchronization, and 7 demonstrated
improved systemic ventricular function. It is important to
note that none of the 11 patients with primarily inserted
biventricular pacemaker system had signs of systemic
1298 October 25, 2016
ventricular failure at the latest follow-up. On the basis of
these data, we recommend that strong consideration be
given to primary biventricular pacing in all patients with
ccTGA who develop heart block.
Cardiac Resynchronization Therapy
Cardiac resynchronization therapy (CRT) has been
shown to be an effective potential option in the treat-
ment of patients with systemic RV dysfunction.9,33 Ven-
tricular dyssynchrony is not uncommon for ccTGA,
particularly those requiring pacing resulting from perma-
nent complete heart block, and a significant percent of
patients may benefit from its correction. In a study of
49 adult patients with ccTGA with systemic RV, Diller et
al33 found a significant interventricular conduction delay
(QRS >120 milliseconds) in 37% of patients. Jauvert et
al9 applied CRT by a combined transvenous and epicar-
dial approach in 7 symptomatic patients with a systemic
RV. All patients had ventricular dyssynchrony caused by
delayed septal wall contraction; therefore, the septum
and RV free wall were stimulated synchronously, with the
goal of resynchronizing a maximum amount of myocar-
dium. Significant improvement in RV mechanical function
and clinical and functional status was seen in all cases.
The largest multicenter, clinical trial on the application of
CRT in patients with a systemic RV was reported by the
Dubin et al.34 CRT was applied in 17 patients (13 patients
with ccTGA and 4 with atrium-level correction of simple
transposition of the great arteries [Senning or Mustard
procedures]). A significant decrease in QRS duration,
increase in systemic RV ejection fraction, and clinical
improvement was observed in 13 patients. However, the
number of patients in this trial is still small, and whether
CRT will have similar results in larger groups of patients
with ccTGA remains unknown. CRT, however, can be a
valuable option for the management of patients with sys-
temic RVs and documented ventricular dyssynchrony,
but further application in large groups is necessary to
confirm its effectiveness.
Mechanical Circulatory Support
Implantation of a ventricular assist device (VAD) into a
systemic RV in ccTGA has been described in several
reports limited to small groups or single patients.35–37
This approach is typically aimed at a bridge for trans-
plantation rather than at treatment of heart failure with
subsequent explantation of the device. VADs have 2 sig-
nificant advantages for patients with ccTGA over other
interim procedures as a bridge to transplantation: They
effectively decompress the systemic RV and postpone
further development of noncardiac symptoms of heart
failure, and they are not dependent on TV function, so
patients with severe TR may benefit from their implanta-
tion. Implantation of microaxial VADs compensates for
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106
 Management of Systemic RV Failure in ccTGA

STATE OF THE ART

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Figure 2. Management of adult/adolescent patients with congenitally corrected transposition of the great arter-
ies (ccTGA) with systemic right ventricle (SRV).
CRT indicates cardiac resynchronization therapy; EF, ejection fraction; IVS, interventricular septum; LV, left ventricle; PA, pulmo-
nary artery; RV, right ventricle; RVF, right ventricular failure; TV, tricuspid valve; TR, tricuspid regurgitation; and VAD, ventricular
assist device.

the systemic RV failure, improves the patient’s quality

of life, and reduces the incidence of abdominal wound
dehiscence; thus, the patient has a better chance for
VAD explantation.36,37 Implantation of a VAD into a mor-
phological RV presents a surgical challenge because the
inflow cannula of the device can be obstructed by the
moderator band. Therefore, it should be placed more
posteriorly to avoid this problem. In 2013, Shah et al37
reported the largest series of VAD implantation in pa-
tients with systemic RVs. Six adult patients with systemic
RVs (3 patients with ccTGA) underwent implantation of a
VAD into the systemic RV. There was 1 early in-hospital
death; 1 patient underwent heart transplantation; and
the others were either waiting for heart transplantation
or listed for destination therapy. The longest period of
VAD support was reported as 988 days in this trial.
Pharmacological Management of
Systemic RV Failure and Lifestyle
Medical management of congestive systemic RV failure
is focused on the prevention of the progression of sys-
temic ventricular dysfunction. Basic principles of phar-
macological management do not differ much from the
management of congestive LV failure. Aggressive reduc-
tion of the preload and afterload of the systemic ven-
tricle and an improvement in ventricular contraction are
the main aims of pharmacological treatment.
• Angiotensin-converting enzyme inhibitors and
diuretics (spironolactone, furosemide) are typically
used for preload and afterload reduction.
• Administration of β-blockers (carvedilol, ateno-
lol) is also beneficial in ccTGA but requires close

Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106 October 25, 2016 1299

 Filippov et al
attention because β-blockers increase the risk of
atrioventricular block as a result of pharmacologi-
cally induced conduction delay.
• Cardiac glycosides (digoxin) can be used to sup-
port the systemic RV contractility and ejection
volume, but there are very few, if any, data sup-
porting its use. Again, close attention should be
paid to the risk of bradyarrhythmias and atrioven-
tricular block.
• Management of patients with supraventricular
tachycardia includes emergency treatment with
adenosine, ablation therapy, or long-term antiar-
rhythmic therapy.
• All patients except those with severe RV dysfunction
and decompensated heart failure should be encour-
aged to pursuing an active lifestyle while avoiding
hard physical exertions.
Pregnancy in Women With ccTGA
The latest clinical data demonstrated that most women
with ccTGA can successfully carry a pregnancy to term.
Kowalik and colleagues38 reported outcomes of 20 preg-
nancies in 13 women (median follow-up, 19±15 years).
Nineteen pregnancies (95%) were successful, and there
were no related maternal deaths. One patient required
premature delivery because of deterioration of RV func-
tion; supraventricular arrhythmias occurred in 2 women
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during pregnancy; and 1 patient required temporary
pacing for preexistent heart block. Thus, β-blockers and
cardiac glycosides should be used with extreme caution
in pregnant patients with ccTGA. The rates of hospitaliza-
tion for heart failure and echocardiographic parameters
did not differ much between pregnant and nonpregnant
women at the latest follow-up. Preconception counsel-
ing and regular follow-up during pregnancy are recom-
mended for women with ccTGA.
Conclusions
Progressive systemic RV dysfunction in patients with
ccTGA presents a serious challenge for clinical diag-
nostics and management. Ventricular dysfunction can
progress subclinically during a long period of time and
then result in a rapid and unexpected development of
congestive heart failure. Therefore, regular, thorough
assessment of cardiac function is necessary for timely
and correct decisions. Anatomic correction provides
good outcomes in very challenging cases and remains
a preferable and prospective strategy for the manage-
ment of ccTGA in the pediatric population. Despite the
complexity of the procedure, potential complications,
and need for further surveillance, the long-term results
indicate a superior late outcome. Adult patients with
clinical evidence of advanced progressive congestive
1300 October 25, 2016
heart failure or severe TR present the major challenge.
Anatomic repair strategies are not applicable for most
of these patients. Alternative surgical options may im-
prove systemic RV function for some time but cannot
stop the progression of heart failure. Heart transplanta-
tion remains the only lifesaving option for these very
sick patients. New solutions for this serious problem
will probably come from clinical and laboratory stud-
ies. Novel strategies of management will be supported
by new types of surgical devices, interventional tech-
niques, and medical therapies.
Disclosures
None.
AFFILIATION
From Department of Cardiac Surgery, Boston Children’s Hospi-
tal, Harvard Medical School, Boston, MA.
FOOTNOTES
Circulation is available at http://circ.ahajournals.org.
References
1. Wallis GA, Debich-Spicer D, Anderson RH. Congenitally corrected
transposition. Orphanet J Rare Dis. 2011;14:6–22.
2. Said SM, Burkhart HM, Schaff HV, Dearani JA. Congenitally
corrected transposition of great arteries: surgical options for
the failing right ventricle and/or severe tricuspid regurgita-
tion. World J Pediatr Congenit Heart Surg. 2011;2:64–79. doi:
10.1177/2150135110386977.
3. Duncan BW, Mee RB. Management of the failing systemic right
ventricle. Semin Thorac Cardiovasc Surg. 2005;17:160–169.
doi: 10.1053/j.semtcvs.2005.02.009.
4. Kral Kollars CA, Gelehrter S, Bove EL, Ensing G. Effects of
morphologic left ventricular pressure on right ventricular geom-
etry and tricuspid valve regurgitation in patients with congeni-
tally corrected transposition of the great arteries. Am J Cardiol.
2010;105:735–739. doi: 10.1016/j.amjcard.2009.10.066.
5. Hauser M, Bengel FM, Hager A, Kuehn A, Nekolla SG, Kaemmerer
H, Schwaiger M, Hess J. Impaired myocardial blood flow and
coronary flow reserve of the anatomical right systemic ventricle
in patients with congenitally corrected transposition of the great
arteries. Heart. 2003;89:1231–1235.
6. Hauser M, Meierhofer C, Schwaiger M, Vogt M, Kaemmerer H,
Kuehn A. Myocardial blood flow in patients with transposition
of the great arteries: risk factor for dysfunction of the mor-
phologic systemic right ventricle late after atrial repair. Circ J.
2015;79:425–431. doi: 10.1253/circj.CJ-14-0716.
7. Hornung TS, Bernard EJ, Celermajer DS, Jaeggi E, Howman-Giles
RB, Chard RB, Hawker RE. Right ventricular dysfunction in congen-
itally corrected transposition of the great arteries. Am J Cardiol.
1999;84:1116–1119, A10.
8. Grewal J, Crean A, Garceau P, Wald R, Woo A, Rakowski H, Silver-
sides CK. Subaortic right ventricular characteristics and relation-
ship to exercise capacity in congenitally corrected transposition
of the great arteries. J Am Soc Echocardiogr. 2012;25:1215–
1221. doi: 10.1016/j.echo.2012.08.014.
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106

9. Jauvert G, Rousseau-Paziaud J, Villain E, Iserin L, Hidden-Lucet F,
Ladouceur M, Sidi D. Effects of cardiac resynchronization therapy
on echocardiographic indices, functional capacity, and clinical
outcomes of patients with a systemic right ventricle. Europace.
2009;11:184–190. doi: 10.1093/europace/eun319.
10. Rutledge JM, Nihill MR, Fraser CD, Smith OE, McMahon CJ, Bezold
LI. Outcome of 121 patients with congenitally corrected transpo-
sition of the great arteries. Pediatr Cardiol. 2002;23:137–145.
doi: 10.1007/s00246-001-0037-8.
11. Scherptong RW, Vliegen HW, Winter MM, Holman ER, Mulder
BJ, van der Wall EE, Hazekamp MG. Tricuspid valve surgery in
adults with a dysfunctional systemic right ventricle: repair or
replace? Circulation. 2009;119:1467–1472. doi: 10.1161/
CIRCULATIONAHA.108.805135.
12. Dobson R, Danton M, Nicola W, Hamish W. The natural and un-
natural history of the systemic right ventricle in adult survivors.
J Thorac Cardiovasc Surg. 2013;145:1493–501; discussion
1501. doi: 10.1016/j.jtcvs.2013.02.030.
13. Winter MM, Scherptong RW, Kumar S, Bouma BJ, Tulevski II, Tops
LF, Roest AA, Vliegen HW, de Roos A, Groenink M, Mulder BJ.
Ventricular response to stress predicts outcome in adult patients
with a systemic right ventricle. Am Heart J. 2010;160:870–876.
doi: 10.1016/j.ahj.2010.07.015.
14. Barron DJ, Jones TJ, Brawn WJ. The Senning procedure as part
of the double-switch operations for congenitally corrected trans-
position of the great arteries. Semin Thorac Cardiovasc Surg
Pediatr Card Surg Annu. 2011;14:109–115. doi: 10.1053/j.
pcsu.2011.01.005.
15. Malhotra SP, Reddy VM, Qiu M, Pirolli TJ, Barboza L, Reinhartz O,
Hanley FL. The hemi-Mustard/bidirectional Glenn atrial switch pro-
cedure in the double-switch operation for congenitally corrected
transposition of the great arteries: rationale and midterm results.
J Thorac Cardiovasc Surg. 2011;141:162–170. doi: 10.1016/j.
jtcvs.2010.08.063.
Downloaded from http://ahajournals.org by on November 24, 2021
16. Winlaw DS, McGuirk SP, Balmer C, Langley SM, Griselli M, Stüm-
per O, De Giovanni JV, Wright JG, Thorne S, Barron DJ, Brawn WJ.
Intention-to-treat analysis of pulmonary artery banding in conditions
with a morphological right ventricle in the systemic circulation with
a view to anatomic biventricular repair. Circulation. 2005;111:405–
411. doi: 10.1161/01.CIR.0000153355.92687.FA.
17. Cools B, Brown SC, Louw J, Heying R, Meyns B, Gewillig M.
Pulmonary artery banding as “open end” palliation of systemic
right ventricles: an interim analysis. Eur J Cardiothorac Surg.
2012;41:913–918. doi: 10.1093/ejcts/ezr078.
18. Myers PO, del Nido PJ, Geva T, Bautista-Hernandez V, Chen P,
Mayer JE Jr, Emani SM. Impact of age and duration of banding on
left ventricular preparation before anatomic repair for congenitally
corrected transposition of the great arteries. Ann Thorac Surg.
2013;96:603–610. doi: 10.1016/j.athoracsur.2013.03.096.
19. Bautista-Hernandez V, Marx GR, Gauvreau K, Mayer JE Jr, Cec-
chin F, del Nido PJ. Determinants of left ventricular dysfunction
after anatomic repair of congenitally corrected transposition of
the great arteries. Ann Thorac Surg. 2006;82:2059–2065. doi:
10.1016/j.athoracsur.2006.06.045.
20. Gaies MG, Goldberg CS, Ohye RG, Devaney EJ, Hirsch JC, Bove
EL. Early and intermediate outcome after anatomic repair of
congenitally corrected transposition of the great arteries. Ann
Thorac Surg. 2009;88:1952–1960. doi: 10.1016/j.athorac-
sur.2009.08.014.
21. Hiramatsu T, Matsumura G, Konuma T, Yamazaki K, Kurosawa
H, Imai Y. Long-term prognosis of double-switch operation for
congenitally corrected transposition of the great arteries. Eur J
Cardiothorac Surg. 2012;42:1004–1008. doi: 10.1093/ejcts/
ezs118.
22. Langley SM, Winlaw DS, Stumper O, Dhillon R, De Giovanni JV,
Wright JG, Miller P, Sethia B, Barron DJ, Brawn WJ. Midterm
results after restoration of the morphologically left ventricle to
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106
Management of Systemic RV Failure in ccTGA
the systemic circulation in patients with congenitally corrected
transposition of the great arteries. J Thorac Cardiovasc Surg.
2003;125:1229–1241.
23. Hraška V, Mattes A, Haun C, Blaschczok HC, Photiadis J, Murin
P, Zartner P, Asfour B. Functional outcome of anatomic cor-
rection of corrected transposition of the great arteries. Eur
J Cardiothorac Surg. 2011;40:1227–1234. doi: 10.1016/j.
ejcts.2011.01.077.
24. Lim HG, Lee JR, Kim YJ, Park YH, Jun TG, Kim WH, Lee CH, Park
HK, Yang JH, Park CS, Kwak JG. Outcomes of biventricular re-
pair for congenitally corrected transposition of the great arteries.
Ann Thorac Surg. 2010;89:159–167. doi: 10.1016/j.athorac-
sur.2009.08.071.
25. Murtuza B, Barron DJ, Stumper O, Stickley J, Eaton D, Jones
TJ, Brawn WJ. Anatomic repair for congenitally corrected trans-
position of the great arteries: a single-institution 19-year experi-
ence. J Thorac Cardiovasc Surg. 2011;142:1348–1357.e1. doi:
10.1016/j.jtcvs.2011.08.016.
26. Bautista-Hernandez V, Myers PO, Cecchin F, Marx GR, Del
Nido PJ. Late left ventricular dysfunction after anatomic repair
of congenitally corrected transposition of the great arteries.
J Thorac Cardiovasc Surg. 2014;148:254–258. doi: 10.1016/j.
jtcvs.2013.08.047.
27. Myers PO, Bautista-Hernandez V, Baird CW, Emani SM, Marx GR,
STATE OF THE ART
del Nido PJ. Tricuspid regurgitation or ebsteinoid dysplasia of the
tricuspid valve in congenitally corrected transposition: is valvulo-
plasty necessary at anatomic repair? J Thorac Cardiovasc Surg.
2014;147:576–580. doi: 10.1016/j.jtcvs.2013.10.014.
28. Talwar S, Ahmed T, Saxena A, Kothari SS, Juneja R, Airan B. Mor-
phology, surgical techniques, and outcomes in patients above
15 years undergoing surgery for congenitally corrected trans-
position of great arteries. World J Pediatr Congenit Heart Surg.
2013;4:271–277. doi: 10.1177/2150135113476717.
29. Koolbergen DR, Ahmed Y, Bouma BJ, Scherptong RW, Brugge-
mans EF, Vliegen HW, Holman ER, Mulder BJ, Hazekamp MG. Fol-
low-up after tricuspid valve surgery in adult patients with systemic
right ventricles. Eur J Cardiothorac Surg. 2016;50:456–463. doi:
10.1093/ejcts/ezw059.
30. Hraska V, Duncan BW, Mayer JE Jr, Freed M, del Nido PJ, Jonas
RA. Long-term outcome of surgically treated patients with cor-
rected transposition of the great arteries. J Thorac Cardiovasc
Surg. 2005;129:182–191. doi: 10.1016/j.jtcvs.2004.02.046.
31. Mongeon FP, Connolly HM, Dearani JA, Li Z, Warnes CA. Con-
genitally corrected transposition of the great arteries ventricular
function at the time of systemic atrioventricular valve replace-
ment predicts long-term ventricular function. J Am Coll Cardiol.
2011;57:2008–2017. doi: 10.1016/j.jacc.2010.11.021.
32. Hofferberth SC, Alexander ME, Mah DY, Bautista-Hernandez V,
del Nido PJ, Fynn-Thompson F. Impact of pacing on systemic
ventricular function in L-transposition of the great arteries.
J Thorac Cardiovasc Surg. 2016;151:131–138. doi: 10.1016/j.
jtcvs.2015.08.064.
33. Diller GP, Okonko D, Uebing A, Ho SY, Gatzoulis MA. Cardiac
resynchronization therapy for adult congenital heart disease pa-
tients with a systemic right ventricle: analysis of feasibility and
review of early experience. Europace. 2006;8:267–272. doi:
10.1093/europace/euj048.
34. Dubin AM, Janousek J, Rhee E, Strieper MJ, Cecchin F, Law
IH, Shannon KM, Temple J, Rosenthal E, Zimmerman FJ, Davis
A, Karpawich PP, Al Ahmad A, Vetter VL, Kertesz NJ, Shah M,
Snyder C, Stephenson E, Emmel M, Sanatani S, Kanter R, Ba-
tra A, Collins KK. Resynchronization therapy in pediatric and
congenital heart disease patients: an international multicenter
study. J Am Coll Cardiol. 2005;46:2277–2283. doi: 10.1016/j.
jacc.2005.05.096.
35. Huang J, Slaughter MS. HeartWare ventricular assist device place-
ment in a patient with congenitally corrected transposition of the
October 25, 2016 1301
 Filippov et al
great arteries. J Thorac Cardiovasc Surg. 2013;145:e23–e25.
doi: 10.1016/j.jtcvs.2012.11.008.
36. Jacobs S, Rega F, Burkhoff D, Meyns B. The use of a Circu-
Lite micro-pump for congenitally corrected transposition of the
great arteries. Eur J Cardiothorac Surg. 2012;42:741–743. doi:
10.1093/ejcts/ezs308.
37. Shah NR, Lam WW, Rodriguez FH 3rd, Ermis PR, Simpson L, Fra-
zier OH, Franklin WJ, Parekh DR. Clinical outcomes after ventricu-
Downloaded from http://ahajournals.org by on November 24, 2021
1302 October 25, 2016
lar assist device implantation in adults with complex congenital
heart disease. J Heart Lung Transplant. 2013;32:615–620. doi:
10.1016/j.healun.2013.03.003.
3 8. Kowalik E, Klisiewicz A, Biernacka EK, Hoffman P. Pregnancy
and long-term cardiovascular outcomes in women with con-
genitally corrected transposition of the great arteries. Int
J Gynaecol Obstet. 2014;125:154–157. doi: 10.1016/j.
ijgo.2013.10.022.
Circulation. 2016;134:1293–1302. DOI: 10.1161/CIRCULATIONAHA.116.022106