Evaluation of the clinical impact of ventricular dyssynchrony in patients with corrected tetralogy of Fallot

Cardiac resynchronization therapy (CRT) has emerged as a valuable tool in the
management of patients with left ventricular (LV) dysfunction and QRS
prolongation. Left ventricular (LV) dyssynchrony, as effect of intraventricular
conduction defects or bundle branch block causes nonsynchronous LV contractions
and places the failing heart at a further mechanical disadvantage.
Atrial-synchronized biventricular pacing or CRT aims to resynchronize the
failing heart improving myocardial contraction without increased energetics.
In patients with congenital heart disease, heart failure is one of the major
causes of late mortality. The right ventricle (RV) sustaining either the
systemic or pulmonary circulation is of special notice in these patients as, in
contrast to ischemic heart disease, the RV is often the failing ventricle. The
possible negative effects of RV dyssynchrony, as result of right bundle branch
block, on the failing RV are unclear .
CRT has been reported to improve cardiac function as well as quality of life
and life expectancy in the majority of selected patients. Inclusion criteria
for CRT used in large clinical trials are NYHA-class III to IV, QRS-duration
>=120-130 ms and depressed left ventricular ejection fraction <= 35%. However,
20% to 30% of the patients who meet these criteria do not respond to CRT.
To better predict the success of CRT inter-and intraventricular dyssynchrony
was evaluated and recent studies pointed out that the severity of left
ventricular (LV)-dyssynchrony is a good predictor for response to CRT.
Furthermore, studies comparing inter-and LV-dyssynchrony to QRS-duration
revealed that mechanical dyssynchrony may be present in the absence of
QRS-prolongation and that QRS prolongation is more related to interventricular
dyssynchrony as compared to intraventricular dyssynchrony. Therefore,
evaluation of LV dyssynchrony is getting increasingly important in the
selection of adult patients for CRT. Tissue Doppler Imaging (TDI) is the most
widely used tool to assess cardiac dyssynchrony and proved to be a better
predictor for response to CRT as compared to strain-analysis. Recently, Cardiac
Magnetic Resonance imaging (CMR) was used to assess cardiac dyssynchrony and it
was concluded that CMR and TDI provided comparable information on LV
dyssynchrony.
Over the past decades the survival and life expectancy of patients with
congenital heart disease has increased dramatically. In patients with a
corrected congenital heart defect, heart failure is one of the major causes of
late mortality. Failure of the right ventricle is poorly understood, especially
with regard to therapeutical intervention and until recently no evidence-based
therapy for RV failure is available. Data on the role of CRT in the management
of heart failure in patients with a congenital heart defect are scarce. CRT has
been used in the immediate post-operative period after correction of a
congenital heart defect and improved cardiac output and narrowed QRS-duration
was observed. Furthermore, Dubin et al. evaluated the acute effect of CRT in
chronic right ventricular (RV) failure and demonstrated the feasibility of
RV-CRT in improving RV function and decreasing QRS-duration during a clinically
indicated cardiac catheterization.
Reports on the beneficial effects of CRT as treatment for chronic heart failure
in children and adults with a congenital heart defect are limited. Recently, a
retrospective international multicenter study evaluated the use of CRT in
pediatric patients with acquired or congenital heart disease.
One-hundred-and-three pediatric patients in whom CRT was initiated were
included and CRT induced increase in ejection fraction and decreased
QRS-duration. However, inclusion criteria were heterogeneous and only 54% of
the patients met the criteria for CRT in adults.
A substantial part of the study populations of the above mentioned studies
included patients after correction of a tetralogy of Fallot. This well defined
group is of special interest because these patients often develop RV failure in
the presence of right bundle branch block (RBBB) and RV volume overload due to
pulmonary or tricuspid insufficiency. After surgical correction, QRS-duration
is related to right ventricular dilatation as well as increased left
ventricular dimensions. Furthermore, Gatzoulis et al. reported that QRS >= 180
ms is the most sensitive predictor for malignant ventricular arrhythmias and
sudden death. Pulmonary valve replacement (PVR) can be performed to restore
pulmonary valve function and cancel the deleterious effects of pulmonary
insufficiency on cardiac function. After pulmonary valve replacement cardiac
function improves in the majority of patients with a reduction of QRS duration.
Whether this corresponds with improved intraventricular synchronization of the
right ventricle has not been studied. Until now, optimal timing for pulmonary
valve replacement still remains unclear.
RV failure and QRS prolongation (RBBB) remains a common problem long term
after correction of tetralogy of Fallot and other congenital heart defects, but
the indication and the role of CRT remains uncertain. CRT has been reported to
improve ejection fraction and reduce QRS-duration in patients with tetralogy of
Fallot. However, inclusion criteria for initiation of CRT as therapy of heart
failure are not known. Until now, data are lacking on the degree of intra- and
interventricular dyssynchrony and its relation to ventricular size and function
and QRS duration. Currently, in adult patients with ischemic heart disease,
these parameters have become important predictors of success of CRT After
correction of tetralogy of Fallot, long-term follow-up is needed and repeated
evaluation of pulmonary insufficiency and biventricular function is essential.
CMR is nowadays regarded as the optimal tool in the follow-up of this patient
group. Recently, Westenberg et al. reported a new application of CMR. Velocity
encoded MRI was used to assess left ventricular dyssynchrony and it was
concluded that CMR and TDI provided comparable information on LV dyssynchrony.

1. To compare velocity encoded MRI and tissue Doppler echocardiography in the
assessment of cardiac dyssynchrony
2.To define the presence and degree of RV mechanical dyssynchrony in patients
with corrected tetralogy of Fallot with RV dysfunction using velocity encoded
MRI and tissue Doppler imaging
3.To define the effects of pulmonary valve replacement on the degree of
mechanical dyssynchrony of the RV in patients with corrected tetralogy of
Fallot .
Secondary objectives
4.To select possible candidates for CRT in patients with corrected tetralogy of
Fallot and RV failure

prospective patient based study

Echocardiography is a non-invasive and safe imaging tool and poses no risks of
any damage. The burden is minimal as the patient/healthy controls is examined
in the supine position during 30 minutes.
MRI is a non-invasive, safe imaging tool and poses no risks of any damage. The
burden is little: the patient/healthy subject is postioned in the supine
position in the MRI scanner with a narow MRI tunnel during 60-90 minutes.
During this time the subjects favourite music can be played. If there is any
doubt whether or not the subject can undergo the MRI examination, a dummy MRI
scanner (MRI-machine without magnetic field) is available, to test the subjects
ability to undergo the MRI examination.