PREVENT-HF: Prevention of Heart Failure Events With Impedance Cardiography Testing

The course of patients with chronic heart failure is marked by periodic episodes of clinical
decompensation that not only impair the quality of life and may be fatal but also consume
substantial health care resources, primarily due to the costs of hospitalization. Heart
failure management programs have been developed to reduce the frequency and severity of
these clinical events, but their effectiveness may be limited by physicians' difficulty in
identifying patients at imminent risk. Reliable prediction of these events may afford
physicians the opportunity to intervene aggressively and potentially minimize the need for
hospitalization or the risk of a serious adverse outcome.

Noninvasive impedance cardiography (ICG) is a simple test that utilizes changes in thoracic
electrical impedance to measure thoracic fluid content, changes in the duration of cardiac
ejection and the velocity of blood flow within the aorta. ICG has been used to estimate
cardiac output and cardiac filling pressure in patients with or without heart failure (HF).

PREVENT-HF is a randomized prospective study being conducted at up to 35 experienced
investigative centers from the United States, Canada, and Europe. Subjects will be enrolled
within 4-12 days of a discharge from a hospitalization for exacerbation of heart failure,
with screening procedures to occur prior to the enrollment. Following enrollment, subjects
will be randomized in a 1:1 ratio to outpatient management by either clinical assessment
(Standard Care Arm) or ICG in addition to clinical assessment (ICG Arm) during the
enrollment visit. ICG variables will be collected in all subjects but will be blinded in the
Standard Care Arm. Each subject's study participation will last for a minimum of 24 weeks
and a maximum of 52 weeks post-discharge. Four weeks after hospital discharge, subjects will
visit the clinic. Remaining study visits will occur every four weeks thereafter until the
subject has completed the 52-week visit or until the subject has experienced a
hospitalization that has been adjudicated by the Clinical Events Committee as being a heart
failure hospitalization.

In the PREDICT study, a composite ICG score was the most powerful predictor of a short-term
HF event when compared to standard clinical variables. This composite ICG score is provided
for subjects in the PREVENT-HF ICG Arm. If the score indicates a subject is at a higher risk
for a short-term HF event, clinicians will be required to intervene. Clinicians may
intervene if indicated by the subject's clinical status for an intermediate-risk score, and
intervention is not recommended based on the ICG score for lower-risk scores. Compliance to
these guidelines will be tracked.

Inclusion Criteria:

- Discharge within 12 days from a hospitalization with the primary diagnosis of heart
failure

- Age 18 years or older

- Chronic heart failure of at least 2 months' duration due to an ischemic or
nonischemic etiology

- Receiving medications for heart failure that are considered (in the judgment of their
physician) as being appropriate for their clinical status

- Able to acquire data successfully with the BioZ device

- Able and willing to provide written informed consent

Exclusion Criteria:

- Height < 48 inches or > 90 inches (< 120 cm or > 230 cm); weight < 67 lbs or > 341
lbs (<30 kg or >155 kg)

- Acute heart failure due to myocarditis, cor pulmonale, congenital heart disease,
constrictive pericarditis, or hypertrophic, restrictive or obstructive cardiomyopathy

- Presence of severe aortic regurgitation

- Acute coronary syndrome (myocardial infarction or unstable angina) or coronary
revascularization procedure (coronary bypass surgery or angioplasty) within 2 months

- History of resuscitated sudden death, ventricular fibrillation, or hemodynamically
destabilizing VT unless treated with a properly functioning ICD

- One or more episodes of ventricular fibrillation or hemodynamically destabilizing
ventricular tachycardia within the previous 30 days

- Second degree - Mobitz Type II or third degree heart block, unless treated with a
cardiac pacemaker

- Implantation of a left ventricular assist device, hemodynamic monitor, activated
minute ventilation pacemaker, or biventricular pacemaker (cardiac resynchronization
therapy) with the V-to-V interval set at more than 5 milliseconds offset

- Implantation of a CRT (cardiac resynchronization therapy) device within the previous
30 days

- Planned implantation of a CRT within the next 6 months

- Clinician use of intrathoracic impedance data from an implanted pacemaker with this
capability

- Participation in a transtelephonic or internet-based formal monitoring program

- Most recent serum creatinine > 3 mg/dl; any liver function test (ALT, AST or
bilirubin) > 3 times the upper limit of normal; chronic dialysis; or chronic
ultrafiltration

- Plan to serially monitor B-type natriuretic peptide (BNP) or N-terminal prohormone of
B-type natriuretic peptide (NT-proBNP) as part of outpatient management

- Post-discharge management with outpatient infusions

- Pulmonary disease sufficient to significantly limit exercise or requiring long-term
treatment with oral corticosteroids

- Known hypersensitivity or allergies to sensor gel or adhesive; skin lesions that
prohibit adequate sensor placement

- Women known to be pregnant or who are planning to become pregnant in the next 12
months

- Current participation in other investigational drug or device protocols, with the
exceptions of registries and subjects in long-term safety follow-up with no active
treatment for at least 60 days

- Subjects with a disorder other than heart failure that might be expected to
compromise their survival within the next 12 months