RethinQ Study - Evaluating Pacing in Heart Failure Patients

1.0 Problem of Interest

Patients with heart failure have a pumping action of the ventricles in which one ventricle
contracts before the other ventricle. This uncoordinated (unsynchronized) pumping is due to a
delay in the stimulation of the left ventricle because of its increased size. Pacing both the
right and the left side of the heart (or cardiac resynchronization therapy [CRT]) has been
proven to be effective in the treatment of heart failure. Current market-approved devices
combine both pacing (CRT) and shocking (ICD) therapy for patients who have severe heart
failure and are at risk for developing life-threatening heart rhythms. These devices provide
an electrical pacing stimulus to both ventricles at the same time and may help the heart
contract in a more coordinated way and improve heart failure symptoms.

The investigational portion of this trial involves the implantation of a market-approved CRT
implantable cardioverter defibrillator (CRT-D) system in patients who do not meet the current
criteria for a CRT implant. In order to receive a CRT-D implant today, patients must have
heart failure symptoms, have a weakened heart muscle, and have uncoordinated pumping of the
heart. To demonstrate this uncoordinated pumping of the heart, a test (ECG) is done. It is
believed that by using a different test (echocardiogram) to measure whether this
uncoordinated pumping is present, more patients will be identified that will benefit from
CRT-D therapy.

2.0 Study Summary

Testing will be performed to determine if patients are eligible for this study. An EKG
(electrical tracing of the heart) will be performed. They will be asked to complete a 6-
minute hall walk test that will provide information regarding their ability to exercise and
conduct daily activities. An echocardiogram with tissue Doppler imaging (ultrasound of the
heart) will be performed to determine how the heart muscle contracts. Results of this
echocardiogram will determine if patients are eligible to participate in this study.

The device system that will be implanted consists of a St. Jude Medical CRT-D and three
pacing leads (insulted wires that carry electrical energy from the device to the heart). One
lead is placed in the upper right chamber of the heart (atrium), a second lead is placed in
the lower right chamber of the heart (right ventricle) and the third lead is placed within a
vein that runs along the outside of the heart and is positioned at a location near the left
lower chamber of the heart (left ventricle).

A randomization visit will occur approximately 14 days after implant. Patients will be
randomized (like a flip of a coin) to one of two groups. Each patient will have an equal
chance of being randomized to either of the two groups. One group will receive cardiac
resynchronization treatment (CRT ON) and the other group will not receive cardiac
resynchronization treatment (CRT OFF). Patients in the CRT OFF group can receive cardiac
resynchronization treatment at 6 months after randomization if the doctor determines that it
is appropriate.

Prior to randomization and programming of the device, the following tests will be completed:

- Quality of Life Questionnaire - contains 21 questions that provide information as to how
heart failure affects the patient's daily life.

- EKG

- 6-Minute Hall.

- Cardiopulmonary Exercise Stress Testing (CPX) - measures the amount of oxygen used by
your body while exercising on a treadmill and breathing through a special breathing tube

- Echocardiogram

Follow-up visits will occur at 3 and 6 months following randomization and every 6 months
thereafter until the end of the study. The tests performed at the randomization visit
(Quality of Life Questionnaire, EKG, 6 minute hall walk, CPX and echocardiogram) will be
repeated at the 6-month follow-up visit. Additionally, each visit will include a review of
the patient's condition and current medications and an evaluation of the CRT-D device.

3.0 How Will the Research Advance Scientific Knowledge and/or Human Health?

It is hoped that by pacing both lower chambers of the heart in these patients that they will
feel better. They may be able to do more activities with fewer symptoms. In addition, the
information gathered in this study will add to the understanding of treatment options for
patients with heart failure.

4.0 What is the Current Standard of Care?

Alternative treatments to the St. Jude Medical CRT-D system (includes the left heart lead)
currently available include implantation of a standard ICD system and/or treatment with
medications.

Inclusion Criteria:

- Have an approved indication for implantation of an ICD.

- Have advanced HF with a New York Heart Association (NYHA) Classification of III,
despite receiving optimal pharmacological therapy.

- Have a stable heart failure medical regimen.

- Have a left ventricular ejection fraction (LVEF) <= 35%.

- Have evidence of mechanical dyssynchrony as measured by echocardiography using tissue
Doppler imaging or M-mode.

- Have a QRS duration < 130 ms (present in all ECG leads).

- Have the ability to complete exercise stress testing and 6-minute hall walk test, with
the only limiting factors being related to cardiac fitness.

- Have the ability to independently comprehend and complete a quality of life
questionnaire.

- Have the ability to provide informed consent for study participation and be willing
and able to comply with the prescribed follow-up tests and schedule of evaluations.

Exclusion Criteria:

- Have a standard bradycardic indication for pacing.

- Have been previously treated with CRT.

- Have continuous atrial fibrillation [AF] (continuous is defined as AF lasting > 1
month) within 1 year prior to enrollment or have undergone cardioversion for AF in the
past month.

- Have the ability to walk > 450 meters during the 6-minute walk test.

- Have a NYHA Classification of I, II or IV.

- Have symptomatic chronic obstructive pulmonary disease (COPD) as it relates to
exercise ability.

- Have a classification of Status 1 for cardiac transplantation or consideration for
transplantation over the next 6 months.

- Have had a recent myocardial infarction, unstable angina or cardiac revascularization
(percutaneous transluminal coronary angioplasty [PTCA] or coronary artery bypass graft
[CABG]) within 40 days of enrollment.

- Have had a recent cerebrovascular accident (CVA) or transient ischemic attack (TIA)
within 3 months of enrollment.

- Have severe musculoskeletal disorder(s).

- Pregnant or planning for pregnancy in the next 6 months.

- Currently participating in, or have participated in any clinical investigation within
the last 30 days (the only exception being that of a registry trial).

- Have a life expectancy of less than 6 months.

- Less than 18 years of age.