Prospective Observation of Exercise Parameters in Advanced Heart Failure

Cardiopulmonary exercise testing (CPXT) has a long history in the evaluation and management
of cardiovascular diseases, particularly in patients with advanced heart failure.

Cardiovascular exercise testing is a safe, well-developed, and validated method for risk
stratification and objective documentation of exercise capacity in patients with severe
heart failure (1,2). Recent studies have also shown that exercise testing has prognostic
power for heart failure hospitalization and mortality (3,4), but limited published data are
available in a large group of advanced heart failure patients, such as those with cardiac
resynchronization therapy (CRT) and left ventricular assist devices (LVAD)

Advanced or suspected advanced heart failure. Typical patients screened for this study will
be patients who have been referred to the University of Minnesota for evaluation for
advanced heart failure options, such as cardiac transplant or mechanical circulatory
support. This is a somewhat heterogeneous population, but all have been diagnosed by
referring physician as having sufficiently severe heart failure to seek tertiary care. Most
are anticipated to have severely depressed ejection fraction (<30% and typically <20%), but
patients with preserved ejection fraction and either hypertrophy or restrictive
cardiomyopathy will also be eligible. Patients pulmonary hypertension, on any therapy (other
than diuretics alone), are also felt to be at high risk of developing right heart failure
and may also be included. Patients who have already undergone LVAD or cardiac transplant are
also considered to have advanced heart failure and are eligible to participate, regardless
of the severity of their symptoms at the time of enrollment.

Healthy volunteers may be included for comparison.

This is a non-randomized, observational investigation of sub-maximal exercise ventilation
parameters in patient diagnosed with, or suspected to have, advanced heart failure.

Duration of follow-up will be up to five years. Some subjects will undergo only one
exercise test. Patients who present with heart failure but subsequently undergo CRT
implantation, LVAD implantation, or cardiac transplant will be asked to repeat the
submaximal exercise test. The timing between any of these events is unpredictable, so the
duration of follow-up cannot be predicted. Subjects will be followed for change of status
for up to 5 years. The total number of tests that any one person could potentially have is
5 (baseline plus one after each therapy), although we expect that most participants would
not be asked to undergo more than 3 tests.

For patients without a device: Patients start at rest for 2 minutes and will wear a face
mask and breathing parameters are recorded using the SHAPE-HF system (SHAPE Medical St.
Paul, MN) that measures respiratory airflow and the constituent respiratory gases, oxygen
and carbon dioxide. The SHAPE-HF system will continue to monitor and the patient then will
start walking on a treadmill with a variable speed of 1-3 mph and a variable grade of 0-6%.
The total treadmill time will be no more than 10 minutes.

For patients with a device: patients will be at rest and the adjustments of their device
will be made by a study physician or device coordinator, done routinely in clinical
practice. This will take up to 15 minutes and during this time; participants will wear a
face mask and breathing parameters are recorded using the SHAPE-HF system (SHAPE Medical St.
Paul, MN) that measures respiratory airflow and the constituent respiratory gases, oxygen
and carbon dioxide. Device parameters will be returned to baseline settings following this
part of the test.

Sub-maximal exercise testing approximately 30 minutes in duration will be performed on a
treadmill at a slow and constant pace, the speed of the treadmill will range from 1-2 mph
and the grade will range from 0-2% depending on the patient's exercise tolerance. The
exercise will be split into two rounds of exercise up to 15 minutes each. Subjects may rest
as long as they would like between the two tests.

The first round, participants will wear a face mask and breathing parameters are recorded
using the SHAPE-HF system. (See section 13B for sample report).

In the second round, every two minutes, up to 15 minutes, participants will be asked to take
8 breaths using a breathing bag containing a standard mixture of gases (0.7% acetylene, 21%
oxygen, 9% Helium and the balance of nitrogen)-this gas mixture is routinely used in
pulmonary function laboratories to measure lung function and has the same amount of oxygen
as room air. Acetylene mass spectroscopy is then used to measure cardiac output
noninvasively.

Neither the SHAPE-HF system, nor the methods of gas exchange during exercise are
investigational.

Participants who are treated with cardiac resynchronization therapy and/or ventricular
assist device may have minor adjustments made to their device parameters every 2 minutes
during the testing. The adjustments will be made by a study physician or device
coordinator, as mentioned before, done in routine practice. Device parameters will be
returned to baseline settings following the test.

Inclusion Criteria:

1. Age ≥18 years

2. Advanced heart failure suspected or diagnosed

Exclusion Criteria:

1. Inability to ambulate at least one block

2. Angina that has developed or a changed in pattern/symptoms since last physician
visit.

3. Recent life-threatening arrhythmia or diagnosis that suggests high-risk of
exacerbation of arrhythmia with exercise (catecholaminergic polymorphic ventricular
tachycardia, e.g.)

4. LVAD driveline infection or suspected driveline infection

5. Medical activity restriction that precludes ambulation