Optimizing cardiac resynchronization therapy with the use of an implantable heart monitor

Cardiac resynchronization therapy (CRT) has become common practice in patients
with drug refractory heart failure (HF) and cardiac asynchrony. Unfortunately,
approximately one third of the recipients of a CRT-device are non-responders.
Optimization of the device helps to improving the number of responders.
Measurement of changes in pressure over time (dP/dt) of the left ventricle is
still the gold standard for optimization of CRT-devices. However, invasive
dP/dt measurements are complicated, time-consuming, costly and foremost not
without risk for the patient. Therefor there is a need for a non-invasive tool
for recurrent optimization of CRT-devices.

In a pilot study patients scheduled for a regular implantation of a (or
undergoing an upgrade to a) CRT-device will also be implanted with a heart
monitor in the pulmonary artery. This implantable heart monitor (IHM) will
collect data during optimization of the CRT-device. Subsequently, the dataset
collected by the implantable heart monitor (IHM) will be used to determine the
IHM-read out associated with an optimal dP/dt during CRT-optimization.
The aim of the pilot study is to establish if, and so how an IHM can be used
for optimization of CRT-devices.

The present study is a 'pilot study' used as a proof of principle.

Potential issues of concern
Both the CRT-devices and the CardioMEMS sensor are indicated for use in the
proposed patient population. The risks and benefits are well known and not
under examination in the present study. Further information can be found in the
IBs of these devices. Optimizing CRT-devices is also part of our common day
clinical practice and using a pressure wire for this is still the golden
standard and used often. However an optimization is not always performed and in
some clinics this is only done on indication, i.e. cardiac underperformance
after CRT-implant. Therefor it could be argued that the explicit optimization
is a potential concern. Collecting the CardioMEMS sensor data during the
optimization holds no risks or extra burden to the participants and it does not
prolong the optimization. Therefore, the risk analysis will focus on the
optimization itself as it will be performed as standard care in all
participants of the study and not only on indication as is also common.
To be able to perform the invasive optimization a temporary pressure wire has
to be placed in the left ventricle. This is done using conventional fluoroscopy
and it is estimated to take approximately 5 minutes. This amounts to 5 mSv per
participant which is a category IIb (= 1 to 10 mSv) or intermediate risk in
accordance with the ICRP62.

Previous experiences with invasive optimization
These kinds of optimizations usually take 1 hour, are performed at the cathlab
and during which the patient has to lie down on the treatement table while the
measurements take place. The measurements are done using a small pressure
sensitive catheter introduced through the femeral artery into the left
ventricle.
The adverse event with the highest incidence one can expect is a hematoma at
the excess site. Similar studies showed an incidence of 3% of groin hematomas,
i.e. 1 in 33 patients.[Duckett SG, Ginks M, Shetty AK, Bostock J, Gill JS,
Hamid S, Kapetanakis S, Cunliffe E, Razavi R, Carr-White G, Rinaldi CA.
Invasive acute hemodynamic response to guide left ventricular lead implantation
predicts chronic remodeling in patients undergoing cardiac resynchronization
therapy. J Am Coll Cardiol. 2011;58:1128-36] Our own registry at the AMC of
procedures utilizing the blood vessels in the groin shows an incidence of 2%
for all groin complications. These kind of adverse events are usually treated
conservatively with local pressure bandage. In the worse cases the
interventional radiologist is asked to close ongoing bleeding, AV-fistulae or
aneurysms using thombin injections. And if even these measures are unsuccessful
one can imagine that the vascular surgeon has to be consulted.
One can speculate that assuming a supine position on the operating table,
combined with the stress and anxiety for the procedure could cause extra strain
of the heart. This could induce acute heart failure that would require medical
treatment. In our complication registry of pacemaker and ICD implantations this
was seen once in the past year, i.e. 1 in 473 patients, amounting to an
incidence of 0.2%.
Other adverse events have an even lower incidence. However, one can imagine
that every time you put a wire though arteries and in to the left ventricle one
could damage the blood vessels or even the heart itself. Studies dealing with
dP/dt measuring have not encountered these kind of problems. Although
empirically this does not seem to be a problem it can imagined that patients
whose myocardium is pierced by the pressure wire suffer a tamponade. The lion*s
share of cases of tamponade is treated conservatively or if necessary by
putting a small transcutaneous catheter in the pericardial space until the
tamponade is resolved spontaneously. To the best of my knowledge there had
never been a tamponade in the AMC caused by a dP/dt measurement.

Potential benefits
Potential benefits for implanting CRT-devices is common knowledge, the same
goes for the addition of optimization. The potential benefit of implanting the
CardioMEMSTM sensor is twofold. First, the sensor can be used as the early
warning system of HF for which it was designed. Second, if the pilot is
successful the sensor could be used repeatedly to optimize the CRT-device
without any invasive, lengthy and elaborate procedure with pressure wires.

In summary
The risk for adverse events caused by doing dP/dt measuring on a structural
basis instead of only on indication is very limited. Moreover, to reduce this
small risk even further, all measurements will be done under strict observation
using ECG-, blood pressure and oxygen saturation monitoring, performed at our
fully equipped cathlab. Furthermore, there does not seem to be an alternative
for the present study. Finally, the reward (i.e. the development of a reliable,
usable and reusable, non-invasive optimization tool) seem to outweigh the
minimal risk involved in the study.