Radial Strain ECHO-Guided Implantation of Cardiac Resynchronization Therapy

In this study we propose to evaluate the utility of radial strain imaging using speckle
tracking to predict the response to CRT in patients with ischemic cardiomyopathy (ICMP) with
NYHA functional class 2-4 heart failure and a standard guideline-based CRT indication, and to
determine the value of lead localization determined by radial strain imaging in a
prospective, randomized manner. We will compare two randomized groups of CRT recipients
implanted with CRT-D systems. In the control group, implantation will be performed in the
usual manner and the lead will be placed at the discretion of the implanting physician,
preferably at posterolateral LV sites . In the study group, leads will be placed in areas of
latest contraction that lack significant scar, as determined by speckle tracking imaging. The
primary outcome measure for comparison between the 2 groups will be echocardiographic
response (as assessed by percent reduction in left ventricular end systolic volumes) at 6
months post-implantation. In addition, clinical response parameters will also be measured as
secondary end points.

We hypothesize that 1) patients showing greater dyssynchrony and/or discoordination index
with speckle tracking will derive a significantly greater response to cardiac
resynchronization therapy; and 2) patients allocated to the image-guided LV lead placement
group will derive a significantly greater response to CRT than patients in the non- guided
implantation (control) group.

If radial strain imaging proves useful for improving the CRT response rate and identification
of patients likely to respond, it will have important clinical and economic implications by
improving individual outcomes and more effective utilization of constrained health care
resources. Furthermore, if echo-guided lead implantation proves to be effective in reducing
the relatively large non-response rate to cardiac resynchronization therapy, it will likely
result in increased device utilization among eligible heart failure patients.

Specific Aims Aim #1: To show that in patients with ischemic cardiomyopathy, implantation of
a CRT LV lead guided by radial strain imaging results in a significantly greater
echocardiographic and clinical response to cardiac resynchronization therapy compared with
conventional implantation techniques.

Aim #2: To show that speckle tracking strain data can be used to identify the degree of
echocardiographic response to CRT, using both dyssynchrony (time to peak strain ) and
discoordination indices.

Aim #3:

The Paieon substudy will comprise 40 patients enrolled at 3 centers, for whom additional
information mechanical dyssynchrony, using the Paieon CardioGuide motion map, will be
collected during device implantation as detailed below The primary aim of the study is to
relate data of mechanical dyssynchrony obtained from angiography through the Paieon
CardioGuide motion map to dyssynchrony data obtained from the echocardiogram.

The dyssynchrony data will not be available to the treating physicians and will not be used
to direct the LV lead location.

Inclusion Criteria:

- Patients with ischemic CMP based on evidence of prior MI by history, coronary
angiography/revascularization or imaging

- AHA ACC or ESC EHRA Guideline-based indication (Class I or II) for CRT and NYHA class
II-IV heart failure

- ECG wide QRS and :

QRS > 120 msec in NYHA III- IV

OR

CLBBB or QRS > 150 in NYHA =II

- Sinus rhythm predominant rhythm (PAF not an exclusion)

- All must be candidates for De novo CRT-D implantation with LV lead via transvenous
approach or patients previously implanted with pacemaker or ICD with <20% pacing over
the last three months who are undergoing CRT-D upgrade.

- Patient provides informed consent, tolerate a pectoral implant, agree to comply with
the protocol, and maintain scheduled follow-up visits.

Exclusion Criteria:

- Permanent or persistent atrial fibrillation

- Advanced renal disease (Cr >=2.5 mg/dL)

- Advanced comorbidities with life expectancy of <1 year

- Patients on waiting list for heart transplantation

- Requiring intravenous amines (continuous or or intermittent amine drip therapy)

- Severe chronic pulmonary disease (simulating heart failure)

- Severe (untreated) organic mitral valve disease

- Poorly treated hypertension

- History of myocardial infarction < 3 months; unstable angina < 1m, CABG <3 months; PCI
<3 months

- Mechanical TC valve

- Previously implanted CRT system

- Poorly visualized cardiac chamber dimensions in an echocardiogram performed prior to
enrollment - please help us define

- Pregnancy or child-bearing potential in the absence of accepted forms of birth control

- Concurrent enrollment in other study