Journal of the American College of Cardiology
© 2012 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
Timing of Pulmonary Valve
Replacement in Tetralogy of
Fallot Using Cardiac Magnetic
Resonance Imaging
An Evolving Process*
Kathryn W. Holmes MD, MPH
Portland, Oregon
The observation that adults with repaired tetralogy of Fallot
(TOF) outnumber children is a testament to the exponential
improvements in the medical and surgical management of
the disease (1). The first Black-Taussig shunt placement in
1945 (2,3), improved life expectancy from a few months to
years. Lillehei et al. (4) followed with the first open heart
repair in 1954. The current early survival of TOF is excellent,
approximating 90% through the first 2 decades of life. In the
third decade, however, mortality rate increases (5,6) with
residual sequelae truncating long-term life expectancy and
affecting quality of life (7). Risk factors that predict adverse
outcome are: (1) older age of repair; (2) evidence of sustained
ventricular tachycardia or longer QRS duration; (3) and
hemodynamic compromise due to long-term pulmonary
regurgitation with right ventricular (RV) dilation and dysfunction of both right and left ventricles (1, 8 –11).
See page 1005
Whereas earlier age of repair, pulmonary valve preservation,
and limited ventriculotomy are likely to improve long-term
ventricular function and reduce incidence of arrhythmia, the
pulmonary valve is not always easily preserved, necessitating a
long-term strategy for mitigating the impact of pulmonary
regurgitation on the RV.
As with the left ventricle, the RV dilates and hypertrophies in response to volume overload. Early after repair, the
RV stiffness and decreased capacitance of the pulmonary
arteries reduces the impact of pulmonary regurgitation.
With time, the RV becomes more compliant and dilates,
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Department of Pediatric Cardiology, The Johns Hopkins University,
Baltimore, Maryland. The author has reported that she has no relationships relevant
to the contents of this paper to disclose.
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and the increased capacitance of the pulmonary bed exacerbates regurgitation. After years of chronic pulmonary
regurgitation, compensatory mechanisms eventually break
down (12) leading to RV failure, deterioration in left
ventricular function, and increased incidence of arrhythmias
(8,10,12–16). To ameliorate the impact of pulmonary regurgitation, pulmonary valve replacement (PVR) has emerged
as an effective option; however, there appears to be a limit to
improvements as valve replacement in patients with severe
RV dilation does not lead to improved ventricular function
and functional capacity in all cases (17).
Cardiovascular magnetic resonance imaging (CMR) has
evolved as an valuable tool to evaluate RV hemodynamics
(18). Whereas other modalities for measurement of RV function are available, CMR can provide detailed and reproducible
data regarding right and left ventricular volume, function and
severity of regurgitation, and anatomic abnormalities without radiation exposure. CMR markers such as severe RV
dilation and biventricular dysfunction have been described
as independent predictors of death, sustained ventricular
tachycardia, and heart failure (10). In this issue of Journal,
Lee et al. (19) provide a retrospective CMR analysis of 170
patients with TOF who underwent PVR. Optimal outcome
measures were defined as normalization of RV volume and
function by CMR. After PVR, this cohort demonstrated
overall improvement in RV volumes, biventricular function,
tricuspid regurgitation, pulmonary regurgitation, and
functional American Heart Association heart classification.
No change was demonstrated in history of arrhythmia or
oxygen consumption by cardiopulmonary stress testing.
There were 2 deaths related to the PVR with actuarial
survival at 10 years of 97.5 ⫾ 1.6%. Freedom from redo
PVR at 10 years was 74.5% and freedom from valve failure
at 10 years was 50.3 ⫾ 10%. Subgroup analysis on 67
patients with pre- and post-CMR images generated cutoff
values for optimal outcome as defined by normalization of
CMR parameters: normal RV end-diastolic volume index
([EDVI] ⬍108 ml/m2); end-systolic volume index ([ESVI]
⬍47 ml/m2); and ejection fraction ([EF] ⬎49%). Receiveroperating characteristic curves suggest that a pre-operative
RVEDVI of 168 ml/m2 (sensitivity: 74%, specificity: 74%)
and pre-operative RVESVI ⬍80 ml/m2 (sensitivity: 68%,
sensitivity: 68%) are predictors for optimal outcome. A
receiver-operating characteristic curve for right ventricle
ejection fraction (RVEF) was not determined.
This study is now one of several with recommendations
for optimal timing of PVR-based on pre-operative CMR
parameters. Reported RVEDVI for optimal outcome has
fallen from an initial report by Therien et al. (20) of ⱕ170
ml/m2 to ⱕ160 ml/m2 by Oosterhov et al. (21), and finally
Beuchel et al. (22) to ⱕ150 ml/m2. Previously reported
indexed pre-operative systolic volume for optimal outcome
was ⱕ85 ml/m2 by Therien et al. (20) and ⬍90 ml/m2 by
Geva et al. (23). As surgical remodeling may considerably
alter RV diastolic dimension, indexed systolic volume may
1016
Holmes
Timing of PVR in TOF Using CMR
be a more sensitive CMR parameter of success after PVR.
However, sensitivity and specificity of 68% for RVESVI
(74% for RVEDVI) in the current paper by Lee et al. (19)
suggest that a moderate percentage of patients below and
above the cutoff values will not demonstrate optimal outcome based on CMR parameters. In addition, there is
overlap of QRS duration and RVEF in both the optimal
and suboptimal groups. In a prospective study of patients
referred for PVR with or without surgical remodeling
therapy by Geva et al. (23), pre-operative RVESVI ⬍90
ml/m2 and QRS duration of ⬍140 ms were predictors of
optimal post-operative result (CMR normalization of RV
volumes and function). In contrast, a RVEF ⬍45% and
QRS duration of ⱖ160 ms demonstrated evidence of
persistent RV dilation and dysfunction (23). Therefore,
additional measures such as QRS duration, history of
arrhythmia, and symptoms continue to be important in the
evaluation of the pre-operative decision making.
Despite the lack of CMR evidence of ventricular improvement in some cases, short-term clinical benefit with
PVR is well documented (20 –22,24 –28). Unfortunately,
the long-term clinical impacts of PVR are mixed. In a
matched retrospective cohort study by Gengsakul et al. (29),
84 patients’ status after PVR were compared with the status
of patients in a non-PVR group. Even though there was
improvement in New York Heart Association functional
class and symptoms in the PVR group versus the non-PVR
group, results were tempered by no documented differences
in prevalence of sudden cardiac death, ventricular tachycardia, or oxygen consumption. In a similarly designed study of
77 patients with TOF and PVR, Harrild et al. (30)
demonstrated that PVR did not result in improved longterm survival. However, the findings of the Herrild et al.
(30) study are tempered by baseline differences RV size of
the control group compared to the PVR group (RVEDVI ⫽
132 ml/m2 vs. 196 ml/m2). In an earlier study, Therien et al.
(31) suggested that there is a threshold where PVR may not
have benefit. Conversely, electing not to replace a pulmonary valve in patients with severe RV dilation likely leads to
further deterioration of functional clinical status. Knauth et
al. (10) demonstrated by CMR that a RVEDVI z-score ⱖ7
and LVEV ⬍55% or RVEF ⬍45% as independent risk
factors for death, sustained ventricular tachycardia, and
increase in New York Heart Association functional class. At
present, PVR replacement demonstrates evidence of functional improvement (in most cases) balanced by no clear
alteration in life expectancy.
Pulmonary valve replacement is not without risks.
Whereas mortality for PVR is considered acceptable (0% to
2%) (32), major complications and prolonged hospital stay
are prevalent. A trend in earlier PVR will increase the
number of pulmonary valve interventions. Lee et al. (19)
note that 50% of their cohort demonstrated evidence of
pulmonary valve failure or dysfunction at 10 years. In
addition, a previous review of their cohort estimated 80%
requiring reoperation at 10 years (33). Consequently, if the
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September 11, 2012:1015–7
pulmonary valve is replaced at a mean age of 16 to 20 years
(26), most patients will undergo a second valve replacement
by age 30 to 35 years. Determining factors that influence
longevity of valve function are under intense examination
(34). Therefore, the decision for pulmonary valve replacement should be individualized for each patient and thought
to the future regarding the potential for percutaneous valve
replacement should be considered for each case (35). Discussions of the balance between RV preservation versus the
number of potential pulmonary valve interventions continue
to evolve.
Based on pre-operative CMR findings, Lee et al. (19)
support PVR on the basis of RVEDVI ⬎163 ml/m2 or
RVESVI of ⬎80 ml/m2. However, given the failure rate of
pulmonary valves and mixed data regarding long-term
reduction in sudden death, an individual approach to PVR
is mandatory. A large longitudinal multicenter dataset to
further refine best parameters for surgical or percutaneous
PVR as well as provide better evidence for counseling of
expected post-PVR outcomes is clearly needed to assist in
management in patients with TOF.
Reprint requests and correspondence: Dr. Kathryn W. Holmes,
Oregon Health and Science University, Child Development and
Rehabilitation Center, 707 S.W. Gaines Street, Portland, Oregon
97239. E-mail: holmesk@ohsu.edu.
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Key Words: congenital heart disease y magnetic resonance imaging y
pulmonary valve replacement y tetralogy of Fallot.