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Cardiac resynchronization therapy for pediatric heart failure
Jennifer N. Avari, MD, Edward K. Rhee, MD*
From the Division of Pediatric Cardiology, Washington University School of Medicine/St. Louis Children’s Hospital,
St. Louis, Missouri, and *Eller Congenital Heart Center, Heart Lung Institute, St. Joseph’s Hospital and Medical Center,
Phoenix, Arizona.
Introduction
Pre-CRT implant/patient selection
Cardiac resynchronization therapy (CRT) has been studied
extensively and has been shown to improve quality of life
and to increase survival in both ischemic and nonischemic
adult heart failure patients. It has become the standard of
care for symptomatic heart failure patients (New York Heart
Association class III–IV) with depressed systemic ventricular function (ejection fraction ⬍35%) and wide QRS
(⬎120 ms) despite optimal medical therapy. The pediatric
heart failure population is a heterogeneous population comprising cardiomyopathy and congenital heart disease patients.1 The growing number of patients surviving surgical
interventions has contributed to this heterogeneity.
Current guidelines for CRT implantation in pediatric
patients are broadly based on adult criteria. Pediatric patients receiving appropriate medical therapy for heart failure
who have persistently poor cardiac function (measured by
systemic ventricular ejection fraction) and wide QRS for
age typically are referred for CRT evaluation as an alternative to cardiac transplantation. The CRT evaluation can be
divided into three steps: (1) preimplant, (2) implant, and (3)
postimplant. Appropriate patient selection preimplant is
critically important given that use of current adult criteria
for CRT implantation results in a nonresponder rate of 25%
to 30%.2 Lead site selection studies, primarily conducted in
adults with left bundle branch block, have shown that most
patients can be successfully resynchronized from a lateral
left ventricular (LV) lead. This issue has not been addressed
in the pediatric population, in which isolated left bundle
branch block is rare but chronic right ventricular (RV)
apical pacing is common.1 Postimplant issues regarding
CRT optimization, both atrioventricular (AV) and ventriculoventricluar (VV), in adult and pediatric patients have been
discussed, with no clear consensus. This viewpoint addresses concerns facing the pediatric electrophysiologist at
each time point.
For children with two ventricles and a systemic LV, the
established adult criteria for CRT implantation are applicable, with minor adjustments for QRS duration. However,
when confronted with complex congenital heart disease
(systemic RV or univentricular hearts), there are no coherent guidelines.1 Studies suggest that the echocardiographic
presence of mechanical dyssynchrony preimplant, rather
than QRS duration, is an indicator for CRT response.1–3
Mechanical dyssynchrony is assessed using two-dimensional echocardiography with M-mode and more frequently
with tissue Doppler imaging.2 In 2008, the American Society of Echocardiography published their consensus statement on the use of echocardiography for CRT and concluded that the preferred approach is color-coded tissue
Doppler for both the assessment of LV dyssynchrony and
the prediction of outcome.2
The largest multicenter study to date on the role of
echocardiography in evaluating dyssynchrony is PROSPECT
(Predictors of Response to CRT; abstract presented at the
European Society of Cardiology Congress, September
2007).2,4 Although final results are pending, preliminary
data showed that no echocardiographic measure of mechanical dyssynchrony could be used to improve patient selection. In addition, very high levels of interobserver variability (6.5%–72%) indicate a need for further refinement of
both technique and methodology as a modality for diagnosing dyssynchrony.
Real time three-dimensional echocardiography also has
been used in the evaluation of mechanical dyssynchrony.5
Early reports demonstrate that this imaging modality may
correctly identify segments of late contraction; however,
this technology is limited by low spatial and temporal resolution, with frame rates of approximately 20 to 30 frames
per second.2
Using these echocardiographic measures of dyssynchrony for patients with structurally normal hearts is challenging, even more so when evaluating patients with complex cardiac anatomy and geometry. We have used
noninvasive electrocardiographic imaging (ECGI) as an objective means for measuring electrical dyssynchrony. ECGI
uses 250 body surface ECGs and a patient-specific heart–
torso anatomy derived from ECG-gated thoracic computed
KEYWORDS Congenital heart disease; Cardiomyopathy; Cardiac resynchronization therapy; Pediatric patients (Heart Rhythm 2008;5:1476 –1478)
Address reprint requests and correspondence: Dr. Jennifer N. Avari,
Division of Pediatric Cardiology, Washington University/St. Louis Children’s Hospital, NWT, Campus Box 8116, St. Louis, Missouri 63110.
E-mail address: [email protected].
1547-5271/$ -see front matter © 2008 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2008.05.024
Avari and Rhee
Cardiac Resynchronization Therapy for Pediatric Heart Failure
tomography to create epicardial activation isochrones
throughout the ventricle(s). The electrical dyssynchrony index is computed from the ECGI maps as the standard
deviation of activation times at 500 epicardial sites on the
systemic ventricle. ECGI has been successfully and reproducibly used in heart failure patients6 and in pediatric patients with complex congenital heart disease and has been
verified by invasive catheter mapping.7 At our institution,
patients referred for CRT evaluation routinely undergo
ECGI as part of the screening process. By identifying those
patients with a high electrical dyssynchrony index (indicating significant electrical dyssynchrony), we attempt to objectively preselect patients who may benefit from CRT.
Implicit in this approach is the assumption that the observed
mechanical dyssynchrony is largely the result of the antecedent electrical dyssynchrony. We have termed the interval
between electrical activation and regional myocardial contraction as “electromechanical latency.” Using electrical
dyssynchrony as a surrogate for mechanical dyssynchrony
is possible only if electromechanical latency is constant
throughout the ventricle.
Implant/lead site selection
Select placement on the LV lead at the site of latest contraction has been shown to result in greater improvement in
ejection fraction and cardiopulmonary workload.8 In a study
by Becker et al,8 optimal lead location was defined as the
site of or the site immediately neighboring the location of
the latest contraction (as determined by speckle tracking)
before CRT.
Lead site selection in the pediatric population is complicated by their smaller hearts and complex coronary venous
anatomy, which often accompany complex congenital heart
disease. Implantation of CRT devices is complicated, especially when dealing with small hearts and complex anatomy, and often requires a team approach that includes a
pediatric electrophysiologist and a pediatric cardiothoracic
surgeon. Many pediatric centers electively place epicardial
systemic ventricular leads. Historically, leads have been
placed in a left lateral position or, if a pacing system is in
place, 180° apart from the existing ventricular lead.1
Pre-CRT ECGI can be used to identify segments of late
electrical depolarization as well as scar, lines of slow conduction, and block.6 In 2006, Jia et al6 demonstrated that
ECGI was helpful not only in determining areas of late
electrical depolarization but also in identifying these other
important electrophysiologic properties of the ventricle.
Identifying these regions preimplant can aid in selecting a
suitable location for resynchronization pacing to promote
electrical synchronicity. However, electrical synchrony
does not always correlate with mechanical synchrony.6 The
delay from epicardial activation to endocardial activation,
or intramural delay, may be significant in advanced heart
disease and has not been systematically studied. Electromechanical latency may account for those patients who are
electrically synchronous but remain mechanically dyssynchronous as described by Jia et al.6 Although tissue Doppler
1477
imaging appears to be the ideal modality for assessing this
parameter, technical obstacles and high interobserver variability have limited the utility of tissue Doppler imaging in
guiding CRT lead placement. Cardiac magnetic resonance
imaging also appears to be a promising imaging modality
for assessing regional ventricular mechanical dyssynchrony;
however, given the current state of pacemaker–magnetic
resonance imaging compatibility, this modality is limited to
only the preimplant phase.
Postimplant/optimization
Adult studies have demonstrated that many patients implanted with CRT and subsequently optimized have performed better than those patients not optimized.9 However,
methods of optimization remain unclear and are institutional
dependent.
AV optimization is routinely performed using mitral
valve Doppler inflow.2 Measuring mitral inflow E and A
waves allows for selection of the optimal AV interval,
which allows for completion of atrial systole (resulting in
maximal preload) while preventing mitral diastolic regurgitation. This technique has been modified for patients with
congenital heart disease by measurement of systemic AV
valve inflow. Interventricular (VV) optimization has remained more ambiguous. Use of tissue Doppler imaging
and tissue strain imaging to minimize segmental mechanical
dyssynchrony is common, but both methods are subject to
image acquisition and acoustic windows. At our institution,
we first acquire 12-lead ECGs under various conditions,
including single ventricular site pacing (RV only, LV only)
and different VV timings, to determine those intervals with
more fused QRS signals. Subsequently, tissue Doppler imaging and tissue strain imaging are performed during the
subset of fused VV intervals to select the interval that
minimizes segmental mechanical dyssynchrony. We do not
limit the scope of the echocardiographic interrogation to the
narrowest QRS complex.
We have also used ECGI to assess post-CRT electrical
dyssynchrony as well as changes in electrical dyssynchrony
under different pacing conditions (Figure 1). This technique, first described in 2006,6 has repeatedly demonstrated
that CRT clinical responders programmed to optimal CRT
conditions have an electrical dyssynchrony index within the
range of normal. Nominal CRT conditions have also shown
a more normalized electrical dyssynchrony compared with
single-site ventricular pacing (whether RV or LV), which
consistently produces high electrical dyssynchrony indices
indicating persistent dyssynchrony.
Limitations
One of the major limitations of ECGI is that it provides only
epicardial data. Intramural delay and electromechanical latency may be quite significant, especially in diseased myocardium as seen in heart failure and structurally abnormal
hearts, and may account for the population of patients who
have electrical synchrony and persistent mechanical dyssyn-
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Heart Rhythm, Vol 5, No 10, October 2008
ure substrates, no studies have determined which substrates
(if any) are more amenable to CRT. The long-term effects of
pediatric CRT remain ambiguous due to the lack of longitudinal studies. The limitations of current echocardiographic techniques for patient selection, lead site selection,
and optimization have been highlighted here and stress the
importance of moving toward more objective methods.
Noninvasive ECGI provides a safe, effective, and objective
measure of electrical timing and underlying electrophysiologic substrate. In the future, the ability to create real-time
patient activation isochrones may lead to a clinical role for
ECGI in CRT optimization.
References
1.
2.
Figure 1 Noninvasive electrocardiographic image from a 6-year-old girl
with complete congenital heart block who had undergone an upgrade from
a dual-chamber pacemaker to cardiac resynchronization therapy (CRT) for
dilated cardiomyopathy and heart failure. After the upgrade, she demonstrated dramatic improvement in clinical symptoms and echocardiographic
findings (including increased ejection fraction from 29% to 55% and
reverse remodeling of LV from an LV end-diastolic dimension z-score of
1.59 to 0.1 and end-systolic z-score of 4.09 to 1.06). The ECG image is
shown for three different pacing conditions: C1 ⫽ CRT-optimal settings,
C2 ⫽ left ventricular pacing only, and C3 ⫽ right ventricular pacing only.
The greatest electrical synchrony is seen in C1, with more pronounced
electrical dyssynchrony in both conditions C2 and C3. The patient’s electrical dyssynchrony (ED) indices demonstrated near normalization of ED
index with CRT pacing and markedly abnormal ED indices in C2 and C3.
chrony. Extension of ECGI to the endocardial surface will
help overcome this difficulty.
Future directions
No dedicated trials to date have investigated patient selection, lead site location, or CRT optimization in the pediatric
population. Given the heterogeneity of pediatric heart fail-
3.
4.
5.
6.
7.
8.
9.
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