Optimization of Cardiac Resynchronization Therapy with a Quadripolar Left Ventricular Lead

Chronic heart failure is a major cause of morbidity and mortality in the
Netherlands. 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, optimal pharmacological therapy, New York Heart
Association (NYHA) functional class II-IV/IV and a left ventricular (LV)
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% of patients do not benefit from
CRT. The effectiveness of CRT is subject to a varied amount of factors, such as
patient selection, device programming and LV lead placement. As we have found
by the first OPTICARE study, the effect of CRT can be optimized by programming
the atrioventricular delay (AVD) and interventricular delay (VVD), resulting in
an improved systolic function expressed by dP/dt. Optimizing the AVD and VVD
can thus improve the hemodynamic effect of CRT, however optimization of these
delays cannot overcome a suboptimal lead position. 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. Lead placement is therefore an important factor
in CRT implantation. LV lead placement is restricted by venous anatomy, lead
stability (e.g. need for wedging), local pacing parameters and phrenic nerve
involvement. The recently developed quadripolar lead has the ability to pace at
four electrodes spaced 47mm apart. The three extra electrodes can overcome
suboptimal conditions at the most distal electrode, the latter being the pace
site of conventional bipolar LV leads. A quadripolar lead can therefore improve
response to CRT.

Finding the optimal site of LV stimulation is a interesting and developing
research field. Novel parameters, depicted from interelectrode delays are of
interest, as the values found directly correlate to lead position. The QLVs is
such a parameter and has shown potential to predict acute hemodynamic response
in several studies. Pacing at a long QLVs (>95) even predicts a favourable
prognosis. This study aims to correlate the QLVs of the four electrodes of a
quadripolair lead to acute hemodynamic response with pressure-volume loops. So
that QLVs can be used as a lead positioning target for future implantations.

The primary objective of the study is to determine whether the intrinsic
electrical delay (QLVs) at a specific pacing site is correlated to acute
hemodynamic response (by percentage increase in strokework, %SW) in CRT with a
quadripolar lead.

Prospective single centre observational study with invasive measurements,
implemented after CRT implantation.

Moreover, MRI images will be obtained before the procedure for calculation of
strain. Myocardial wasted work, derived from pressure-strain curves of optimal
configuration (biventriculair, quadripolar and MPP), is compared to intrinsic
rhytm.

During the CRT implantation procedure, the optimal lead position and pacing
vector of the quadripolar LV lead are determined. The correlation of the
electrical delay at the electrodes (QLVs) and the hemodynamic benefit will be
determined. Invasive measurement of LV pressure and intracavitary volume
(pressure-volume loops) is used. Optimal settings are compared to standard
biventricular (BiV) pacing and to multi point pacing (MPP).

Finally, the beat-to-beat variability of the repolarization (BVR) is determined
by alternating the atrioventricular delay.

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

The PV conductance catheter will be inserted as described above. Femoral
arterial access is a routinely used procedure in the UMC Utrecht department of
cardiology and has been routine practice in the electrophysiological
laboratory. The use of the catheter has known complications. Possible
intraprocedural complications due to insertion of the catheter are cardiac
arrhythmias, which are directly recognized by ECG monitoring and effectively
treated by retracting the catheter or defibrillation. Other, very rare, but
potentially life threatening and/or irrreversibal intra-procedural
complications can occur. Possible intraprocedural complications such as are
cardiac tamponade (treated with a pericardial drain), cerebral vascular
incidents (incidence 0.09%) or coronary artery dissection. However rare
(incidence 0.7 - 2.7%), postoperative complications of arterial catheterization
(e.g. local bleedings and pseudo-aneurysms) are seen. These complications are
not life threatening, are easily recognized by treating nurses or physicians
and can be treated effectively, without permanent damage. Pseudo-aneurysms are
treated with trombone injection, bleedings with pressure on the wound or
operative closure if persistent. Patients are restricted to bed rest for a
period of 90 minutes, after closure of the arterial access with an Angioseal.

Measurement of BVR during alternation of the AV interval will not lead to a
direct benefit to the patient. However, these measurements will add a maximum
of only 5 minutes and cause no harm to the subjects* health.

Strain analysis with MRI will lead to a better understanding of hemodynamic en
mechanical interaction of CRT. Transthoracic echocardiography is a non-invasive
and safe diagnostic tool, and will not cause any risk for the subjects.
However, these measurements will not lead to a direct benefit to the patient.