non-responders of cardiac resynchronization therapy: the effect of left ventricular endocardial pacing and simulated exercise on acute hemodynamic response

Cardiac resynchronisation therapy (CRT) with biventricular pacemakers and
implantable cardiac defibrillators (ICD) has proven to be a valuable therapy in
selected patients with systolic heart failure, ameliorating both morbidity and
mortality. However, with current selection criteria and implant technique,
about 20 tot 30 % of patients remain non-responders. Non-responders might be
due to failing selection criteria or methodology in casu echocardiography.
However, an important number of non-responders may result of sub-optimal
positioning of the left ventricular lead, remote from the site of delayed
activation. Endocardial left ventricular stimulation may ameliorate the
shortcomings of epicardial stimulation. The advantage of an endocardial
approach is the absence of phrenic nerve stimulation as limitation to position
the lead, a more predictable pacing threshold and much less restriction to
position the lead in the area of interest.

This study evaluates the difference in response to CRT between endocardial en
epicardial left ventricular pacing. Secondly, we will evaluate the effect of
simulated exercise by means of intravenous dobutamine on response to CRT and
device optimization.

a prospective, single-centre, nonrandomized study, pilot phase

all patients will undergo standard implantation of a CRT-device. During
procedure the effect of CRT will be evaluated on-table by means of measurement
of LV dP/dtmax according to the standard hospital protocol. In the subgroup of
patients who do not show a response to CRT, temporary left ventricular
endocardial pacing will be performed. In the subgroup of patients who do show
response to CRT, the effect of simulated exercise will be evaluated by means of
intravenous dobutamine.

at baseline a clinical examination, laboratory analysis, 6-minute walking test,
echocardiography and cardiac magnetic resonance imaging will be performed. All
of these examinations will be repeated at 6-months follow-up except for the
cardiac magnetic resonance imaging. It is estimated that the investigations
outlined above will require a maximum of three extra on-site visits. Two blood
samples will be drawn. Two health questionnaires need to be completed by
patient.
The echocardiography is a standard investigation needed to optimize the CRT
device. However, some echocardiographic measurements will be performed after
administration of an ultrasound contrast agent (SonoVue®). For this purpose an
intravenous catheter is needed. When administered in a stable patient
population, SonoVue® is considered a safe product. There is a low risk of
allergic reactions (<0.1%); therefore patients with known allergies to sulphur
will be excluded. Potentially unstable patients with recent hospitalized heart
failure or acute ischemic syndrome will also be excluded.
A subgroup will undergo temporary left ventricular endocardial pacing, which
will take place during routine implantation of the CRT-device. This procedure
will lengthen the implantation with about 20 minutes.
Another subgroup will be administered intravenous dobutamine to simulate
exercise. The standard procedure will be prolonged with about 20 minutes.
Administration of dobutamine can result in chest discomfort or palpitations.