Advanced Image Supported Lef ventricular Lead Placement in Cardiac Resynchronization Therapy

Chronic heart failure is a major cause of morbidity and mortality in the
Netherlands, with a prevalence of 6.2 per 1000 in men and 8.5 per 1000 in
women. In 2010, 29.838 patients were hospitalized due to clinical heart failure
and the death of 6.424 patients was reported as a consequence of heart failure.
Heart failure accompanied by ventricular dyssynchrony, determined by a wide QRS
complex on het electrocardiogram (ECG), is a predictor for worse prognosis. A
wide QRS complex (>120ms) is present in about 25-50% of patients with chronic
heart failure.

According to the most recent guidelines, patients with a wide QRS complex are
found to benefit from pharmacological therapy accompanied by general advice
concerning diet, weight, smoking and exercise. Patients who remain in NYHA
class II or higher despite pharmacological therapy, with a left ventricular
ejection fraction of <35%, are found to benefit from cardiac resynchronization
therapy (CRT). There is a class I level of evidence with a level *A* indication
for CRT in recent guidelines, to reduce morbidity and mortality.

The rationale for CRT is based upon the observation that the presence of
ventricular dyssynchrony (a wide QRS complex) can induce systolic dysfunction
and thereby worsen heart failure. To correct ventricular dyssynchrony, three
pacing leads are implanted via a transvenous approach and connected to the CRT
device. One electrode is positioned in the right atrial appendage or
interatrial septum, another electrode in the right ventricular (RV) apex and a
third electrode in a venous branch of the coronary sinus, pacing the LV
epicardium. These ventricular leads pace the LV at two contralateral sites,
reducing dyssynchrony. Unfortunately up to 30-45% of patients do not benefit
from CRT. These patients either stabilize or progress in heart failure. The
effectiveness of CRT is subject to a varied amount of factors, such as patient
selection, device programming and LV lead placement. The latter is of major
importance. A MADIT-CRT substudy showed that pacing at a more distal and/or
apical position was a common finding in patients not responding to CRT. As we
have found in the first OPTICARE study, optimization of device settings cannot
overcome a suboptimal lead position. Moreover, lead placement in a targeted
area of latest mechanical contraction and away from myocardial infarction,
determined by speckle tracking echocardiography, improves response and
prognosis. Multiple studies have advocated the adverse effects of pacing in or
near an area of myocardial infarction. Lead placement is therefore an important
factor in CRT implantation. LV lead placement is however restricted by venous
anatomy, lead stability (e.g. need for wedging), local pacing parameters,
fibrosis and/or infarct location, and phrenic nerve involvement. Determining
the optimal position can therefore be difficult.

Improving LV lead position during implantation, is therefore of importance.
Currently, the optimal lead position is based on the preference of the
cardiologist. The implanting physician has restricted information on the
optimal position. Pre-implantation knowledge of infarct location, combined with
pacing and phrenic nerve thresholds and the visualized coronary venous anatomy
give a limited insight in possibilities and restrictions. Based on avoiding
known predictors, as an apical position, estimated infarct location and phrenic
nerve thresholds during stimulation, the lead is placed in a suitable vein.

Information on infarct location, latest contracting area, and phrenic nerve
position in relation to cardiac venous anatomy, before and during implantation,
could improve the final LV lead position. MRI can provide all these aspects,
fused with a 3D rotational venogram and fluoroscopy images during implantation.
MRI with delayed enhancement imaging can provide information on infarct
location, size and transmurality. MRI-tagging can give information on
myocardial deformation and thereby the latest contracting area. Lastly,
location of the phrenic nerve can be imaged by detailed MRI imaging with tissue
characterization. Reconstruction of the information provided by MRI can give
the implanting physician a detailed overview, for clinical decision making.
Moreover, by real time fusion of 3D reconstruction of MRI with a rotational
venogam by fluoroscopy during implantation, the implanting physician can
determine the optimal lead position. After imaging cardiac venous anatomy, the
cardiologist can choose which side branch of the coronary sinus is ideal for LV
lead placement.

Software for fusion of MRI and CT with a 3D rotational venogram is currently
developed by CART-Tech (CART-Tech B.V., Utrecht, the Netherlands). The
dedicated software package (CARTBox 3) of this spin-off scientific company of
the UMC Utrecht will be used for the study. Its features will be continuously
developed during the study. Specific additions for phrenic nerve visualization
by CT and myocardial deformation results of MRI-tagging will be made during the
study and tested in subgroups. A final software package will be used in a small
population to test the feasibility of CARTbox for CRT implantation purposes.

Primary Objective:
-To test the feasibility of MRI and CT fusion with 3D rotational venogram /
fluoroscopy for left ventricular lead positioning in CRT.

Secondary Objectives:
-Visualize the location and distance to LV lead position of MRI determined scar
tissue combined with 3D rotational venogram / fluoroscopy images during CRT
implantation.
-Visualization and location of the left phrenic nerve, by MRI fusion with 3D
rotational venogram / fluoroscopy, in relation to cardiac anatomy and LV lead
position.
-Determine the latest contracting region by MRI-tagging analysis and
applicability in LV lead positioning, by MRI fusion with 3D rotational venogram
/ fluoroscopy.

The ADVISE-CRT study is an observational pilot study. The feasibility of
magnetic resonance imaging (MRI) and computed tomography (CT) based left
ventricular lead positioning in CRT is evaluated. As experience needs to be
gained and data needs to be gathered, a step-wise approach will be implemented.
Steps will be used to test specific features of MRI and CT fusion with
fluoroscopy images during implantation. An additional aspect of MRI or CT
imaging will be added at each step. Every step will be executed in three
patients The fusion of myocardial scarring, detected with MRI by delayed
enhancement imaging, with fluoroscopy will be the first step (MRI). The second
step will be incorporation of MRI-tagging with detection of the latest
contracting segment (MRI). The third step will incorporate visualization of the
phrenic nerve (CT). A final review group of 6 patients will be the last step,
in which the LV lead position will be decided based on the MRI fused images.

In the final review group of 6 patients, the cardiologist will use the 3D
venogram and fused MRI and CT images during CRT implantation, to optimize the
LV lead position.

The risk and/or complications of the CRT-D implantation itself are not
additional to the study, as the CRT-D implantation with a quadripolar lead is a
standard procedure in the UMC Utrecht.

During implantation an 3D venogram is made, which replaces commonly made 2D
fluoroscopy images. There may be a slightly increased radiation and/or contrast
burden. However, the effects of the relatively small increase will be
negligible.

The MRI scan is standard care in patients planned for CRT implantation. The
additional images prolong the scan duration and therefore cause a minor burden.
The CT scan implemented in the last two phases causes an increased risk due to
radiation and contrast.The burden of these risks is small.

The study can ameliorate the response of patients to CRT. By fusing MRI and/or
CT images with fluoroscopy during LV lead positioning, the implanting physician
can choose a position which would benefit LV function. A lead position with
away from the infarct area, away from phrenic nerve involvement and closest to
or in the latest activated area will improve LV pump function. An improved
response to CRT can improve quality of life and prognosis of heart failure
patients. Especially patients with myocardial infarction and/or coronary artery
stenosis (ischemic cardiomyopathy. As these patients are more often
non-responders to CRT.

The study may also improve the procedure itself. With increased knowledge of an
optimal lead position during implantation, future procedures can be conducted
more easily. The implanting physician can choose a target vessel for optimal
lead position. It can therefore shorten the procedure and prevent potential
complications of prolonged procedures.