ReachPR Trial: Restoration of AV coupling by Cardiac Resynchronization Therapy in heart failure patients with prolonged PR interval

Prolongation of the electrocardiographic PR interval (PR interval > 200ms; also
known as first-degree atrioventricular block) is frequently encountered in
clinical practice and is generally considered as a benign sign. However, there
is increasing evidence that a prolonged PR interval results in poor hemodynamic
performance with elevated left ventricular (LV) end-diastolic pressures
evidenced by diastolic mitral regurgitation. Previous studies also associated a
prolonged PR interval with a substantially increased risk of future atrial
fibrillation (AF) and pacemaker-implantation, and increased risk of heart
failure (HF) hospitalization and death. These risks stress the importance of
proper atrioventricular (AV) coupling. Shortening of the PR interval may be
especially important in HF patients. Shortening of the PR interval can be
obtained by AV pacing. A possible adverse effect of ventricular pacing is that
it results in ventricular dyssynchrony possibly leading to worsening cardiac
function. This effect may be prevented by applying atrio-biventricular pacing.
Data from several previous (sub)studies suggested this.

The purpose of this study is to investigate the acute hemodynamic effects of
restoration of AV coupling by atrio-biventricular pacing in patients with HF
and prolonged PR interval.

This study will be a multi-center, exploratory, prospective interventional,
non-randomized acute hemodynamic study, using patients as their own controls.

Extra hemodynamic measurements will be performed during CRT implantation
(invasive) and after approximately one to two weeks (echocardiographic
protocol).

The patients are candidates for an ICD device in whom cardiac resynchronization
therapy (CRT) can be considered according to current guidelines. Patients in
the present study will receive a CRT-defibrillator (CRT-D). The risk and/or
complications of the CRT-D implantation are not additional for this study.
After the implantation, acute invasive hemodynamic measurements will be
performed with a pressure-volume catheter, which is inserted via the femoral
artery and adds approximately 30 minutes to the standard procedure. We need an
extra radiation dose of approximately 50mGy to place the pressure-volume
catheter in the LV cavity. Local vascular complications of femoral artery
puncture like bleeding or damage to the vessel wall may occur but are rare. The
non-invasive echocardiographic protocol one to two weeks after implantation
will add approximately 45 minutes to the routine outpatient clinic visit. The
patients don*t have to visit the clinic outside the routine outpatient clinic
visits before and after a CRT-D implantation. The patients will have the
potential direct benefit from the procedure, by finding the patient*s specific
optimal (AV) settings and thereby reducing above described risks of a prolonged
PR interval. In case of a worse hemodynamic performance due to the procedure,
the CRT-D will be programmed to back up pacing and there is no harm for the
patient outside the above subscribed extra measurements.