Trial to Evaluate Safety And Effectiveness of Mechanical Circulatory Support in
Patients with Advancing Heart Failure (TEAM-HF)

Patients with heart failure (HF) suffer from a high degree of morbidity and
mortality. Left ventricular device (LVAD) therapy has become the standard of
care for the treatment of advanced HF patients who are deemed to be dependent
on continuous intravenous inotropes, extending life expectancy, enhancing
overall quality of life, and improving functional capacity. However, use of
LVADs in ambulatory, non-inotrope dependent advanced HF population is limited.
Persistent pulmonary hypertension (PH) secondary to left ventricular failure
has emerged as a predictor of increased mortality risk for patients refractory
to maximally tolerated guideline directed medical therapy (GDMT). In these
patients, left ventricular failure with refractory PH may represent objective
criteria to identify advanced HF requiring heart replacement therapies such as
LVAD.

The TEAM-HF trial consists of two arms: a Randomized Arm and a Single Arm
Registry.

TEAM-HF Randomized Arm:
The objectives of the Randomized Arm are two-fold:
1) Demonstrate improvement in survival when non-inotrope dependent advanced HF
patients are treated with the HeartMate 3* left ventricular assist system
(LVAS) compared to being managed on medical therapy alone; and
2) To establish disease-state criteria to trigger referral for a HeartMate 3
LVAS.

TEAM-HF Single Arm Registry:
The objective of the Single Arm Registry is to examine, in patients with lower
PAP, the impact of delayed HM3 LVAS implantation on survival and adverse
events.

TEAM-HF Randomized Arm:

The TEAM-HF The TEAM-HF Randomized Arm is a prospective, randomized, open-label
study of LVAD vs continued GDMT in non-inotrope dependent HF patients with
refractory PH. Refractory PH for this study is defined as mPAP >= 30 mmHg and
determined utilizing the CardioMEMS HF System to identify patients at elevated
risk of mortality. All subjects enrolled will be non-inotrope dependent HF
patients who are already implanted with a CardioMEMS PA Sensor OR will be
implanted with the CardioMEMS PA Sensor after enrollment.

Patients will be randomized in a 1:1 ratio into one of two groups:
• HM3 Group: HeartMate 3 LVAS
• Control Group: Continued GDMT

For patients already implanted with a CardioMEMS PA Sensor: after screening
procedures and signing the Informed Consent Form, subjects will complete
baseline assessments. Upon meeting randomization criteria, patients who have
received GDMT with optimal doses for at least 30 of the last 90 days will be
randomized.

For patients requiring a CardioMEMS PA Sensor implant: randomization will take
place after a 3-months period of optimization of GDMT. Patients meeting all
inclusion and randomization criteria and no exclusion criteria with refractory
PH (mPAP >= 30mmHg) will be randomized.

TEAM-HF Single Arm Registry:

The TEAM-HF Single Arm Registry is a prospective, single-arm, open-label
registry of non-inotrope dependent HF patients responsive to GDMT (mPAP < 30
mmHg). All subjects enrolled will be only non-inotrope dependent HF patients
who will be implanted after enrollment with the CardioMEMS PA Sensor. Patients
with an existing CardioMEMS PA Sensor implant will not be enrolled in the
TEAM-HF Single Arm Registry. After screening procedures and signing the
Informed Consent Form, subjects will complete baseline assessments. After a
3-month period of optimization of GDMT, patients with a mPAP < 30 mmHg
(considered responsive to GDMT) meeting all Single Arm Registry criteria may be
enrolled in the TEAM-HF Single Arm Registry.

All investigators involved in the conduct of the clinical investigation will be
qualified by education, training, or experience to perform their tasks and this
training will be documented appropriately. The study will allow patients within
the Control Group and the Single Arm Registry to receive delayed LVAD treatment
and all transplant eligible patients will have the option to receive heart
transplantation during the study duration. Follow up will continue until
subjects complete their 5-years visit even in the event of a patient receives
an LVAD or transplant. The expected duration of enrollment is approximately 3
years. The total duration of the clinical investigation is expected to be
approximately 8 years

Subject is willing and able to be implanted with the HeartMate 3 LVAS if
randomized to HM3 group.

HeartMate 3* Left Ventricular Assist System (LVAS)

The HeartMate 3 LVAS includes equipment and materials that together comprise a
medical device designed to provide therapeutic benefit to those affected with
advanced HF. In service, the LVAS assumes some or all of the workload of the
left ventricle, thereby restoring the patient's systemic perfusion while
palliating the underlying pathology.

HM3 Indications for Use:
In Europe, the HM3 LVAS is intended to provide long term hemodynamic support in
patients with advanced, refractory left ventricular HF. It is intended either
for temporary support, such as a bridge to cardiac transplantation (BTT), or as
permanent destination therapy (DT) and it is intended for use inside or outside
the hospital.

For patients requiring implantation of a CardioMEMS PA sensor, randomization
will occur after a 3-month period of GDMT optimization. Patients with
refractory PH who meet all inclusion and randomization criteria and no
exclusion criteria (mPAP >= 30 mmHg) will be randomized.


The CardioMEMS* HF System

The CardioMEMS HF System provides pulmonary artery hemodynamic data used for
the monitoring and management of HF patients. The system measures change in PAP
which physicians use to initiate or modify HF treatment.

CardioMEMS HF System Indications for Use: In Europe, the CardioMEMS HF System
is indicated for wirelessly measuring and monitoring PAP and heart rate in New
York Heart Association (NYHA) Class III HF patients who have been hospitalized
for HF in the previous year. The hemodynamic data are used by clinicians for HF
management and with the goal of reducing HF hospitalizations.

The risks associated with the implantation of CardioMEMS HF system and
HeartMate 3 are the same as if they were implanted outside the study.
The times of the visits correspond to the normal checks if you had received
these aids outside the study.

There may be some inconveniences with the study tests and procedures.
You may feel tired or out of breath during the walking test (which may not be
per standard of care).
When you have an additional blood test, you may feel pain or discomfort or
bruise where the blood is drawn.
The subject may be anxious when asked to talk about his/her health and when
completing the questionnaires.