Non-invasive Electrocardiographic Imaging of SyncAV with MPP: Understanding Optimized Programming for Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) involves synchronous pacing from the
right ventricle (RV) and left ventricle (LV) transvenously, typically via a
lead placed in a lateral or postero-lateral coronary vein. There is
considerable evidence demonstrating the value of CRT as a treatment for heart
failure (HF) patients with prolonged QRS duration (QRSd). The clinical benefits
of CRT include restoration of ventricular contractile coordination, reverse
remodeling of the LV, reduced mortality rate, as well as improvement in LV
systolic function, exercise tolerance, and quality of life. Additional
improvement has been achieved with the introduction of MultiPoint* Pacing
(MPP), whereby multiple LV sites along the single quadripolar lead are
stimulated to capture a broader region of excitable myocardium.

Many programmable CRT and MPP parameters have been shown to have a significant
impact on clinical outcomes. However, identifying the optimal set of parameters
relies on an accurate assessment of relative cardiac function. Echocardiography
and invasive LV pressure measurements have been considered the gold standard
for direct, comprehensive hemodynamic optimization of CRT, but both are costly,
time consuming, and must occur in clinic. In contrast, the surface electrograms
(ECG) has been introduced as a simpler alternative, as the electrical synchrony
restored by CRT is also registered in the QRS complex. Dyssynchrony is
associated with a broad QRS complex, and vice versa. Accordingly, programming
CRT with the goal of minimizing QRSd, specifically by achieving a fusion of
paced and intrinsic beats, has resulted in superior clinical outcomes.

Conduction delays associated with the cardiac rhythm, and consequently QRSd,
continuously adapt to an ever-changing cardiovascular status. Consequently, the
timing of CRT stimuli must adapt accordingly to sustain optimal synchrony. An
existing Abbott (ABT) feature, SyncAVTM, enables dynamic AV CRT timing
adjustments in order to adapt to changes in intrinsic conduction, resulting in
fusion pacing when properly optimized. If the AV node conduction down the RV is
normal, SyncAV may be programmed to provide LV only pacing and resynchronize
ventricular contraction in patients with left bundle branch block (LBBB).

Stimulation along a quadripolar lead results in heterogeneous LV activation, as
shown by electrocardiography imaging (ECGi). Some preliminary work has
indicated that MPP can improve hemodynamic response, as well as myocardium
activation. Although it has been advocated that MPP captures more LV
myocardium, resulting in faster depolarization, this has not been prospectively
examined and some studies indicate certain individual patients may worsen with
MPP. The effectiveness of MPP could be influenced by local scar, heart size,
morphology and LV lead position, among other factors.

Electrical optimization may play an important role in improving response to
CRT. Attempts typically involve maximizing intrinsic LV electrical delay (qLV)
at the site of pacing, narrowing the QRS, and minimizing LV paced activation
time. Of these, minimizing LV paced activation duration has been shown to
exhibit higher predictive value for CRT response compared to that of either qLV
or QRS narrowing. As MPP is a pacing strategy, this may be an attractive tool
to facilitate LV capture/activation and merits prospective analysis. In
addition, preliminary results suggest that MPP programming may reduce LV-paced
QRS duration beyond that of traditional LV bipolar pacing. However, LV-paced
QRSd reflects biventricular activation and thus a more sensitive tool is
required for this analysis to determine the effect of MPP on LV activation.

A small series utilizing endocardial contact mapping showed that the area of LV
capture and rate of LV activation were impacted by MPP programming(17). Single
beat whole chamber ECGi mapping may provide the strongest evidence of this
effect. Further, the impact of the creation (or resolution) of lines of
functional block with LV (or even RV) pacing is poorly understood. ECGi imaging
facilitates identification of scar, line of block (functional or otherwise).

This clinical study is designed to evaluate the application of SyncAV and MPP
to improve electrical synchrony and to determine the influencing factors on LV
activation in patients receiving CRT using ECGi, which provides single beat,
non-invasive cardiac mapping. The study will be a prospective, multicenter,
single-arm interventional study recruiting approximately 50 patients.

The objective of this clinical study is to evaluate the impact of Multipoint
Pacing (MPP) and SyncAV programming on ventricular electrical activation time
and activation sequence using noninvasive electrocardiographic imaging (ECGi)
in patients receiving cardiac resynchronization therapy (CRT).

The ECGi with SyncAV with MPP study is a prospective, multicenter, single-arm
interventional study designed to evaluate the application of SyncAV and MPP to
improve electrical synchrony and to determine the influencing factors on LV
activation in patients receiving CRT using ECGi which provides single beat,
non-invasive cardiac mapping.

ECGi Data Collection Visit where device interrogation will be performed
including:

• Pacing system information and parameters (impedance, sensing amplitudes, and
programmed pacing settings)
• Record the intrinsic heart rate.
• Record device sensed AV conduction time (RAs-RVs).
• Record device paced AV conduction time (RAp-RVs).
• Using the Merlin programmer record the LV conduction times (RVs-LVs and
RVp-LVs).
• Record qLV, qRV
• Record QuickOpt parameters

Electrical cardiac activation will be recorded from the ECGi system and with
device IEGM recordings during various CRT pacing configurations.

The risks associated with the medical devices used in this clinical
investigation can be found in the corresponding Instructions for Use (IFU). All
devices are CE-marked and will be used in accordance with the approved
indications and IFU. There are no additional risks introduced to study subjects.

There is no anticipated direct clinical benefit for patients participating in
this study. However, it is possible that clinicians will gain information about
the individual*s acute electrical response to a variety of pacing
configurations. It is also possible the information learned could help add to
the body of knowledge regarding acute response to changes in CRT programming
and long term patient response.

The burden for the patient will be the ECG, NT-pro-BNP sample withdrawal, CT
and ECGi which are not standard of care.
If baseline echocardiographic data were taken > 90 days from the scheduled
baseline visit, the baseline echocardiographic data collection will have to be
repeated, with the device off, prior to or on the day of the ECGi Data
Collection Visit.