St. Jude Medical CardioMEMS CM2000 User manual

CardioMEMS™HF System
PA Sensor and Delivery System
Model CM2000
User's Manual

Do not attempt to use the device before also reading and fully understanding the
System Guide.
Carefully inspect all product packaging for damage or defects prior to use. Do not
use product if you see any indication of damage or breach of the sterile barrier.
This device is supplied sterile for single use only. After use, dispose of the Delivery
System. Do not resterilize.
Caution: Federal (U.S.) law restricts this device to sale by or on the order of a
physician.
Unless otherwise noted, ™ indicates that the name is a trademark of, or licensed to, St. Jude Medical or one of its
subsidiaries. ST. JUDE MEDICAL and the nine-squares symbol are trademarks and service marks of St. Jude
Medical, Inc. and its related companies. © 2014 St. Jude Medical, Inc. All Rights Reserved
2

Contents
Description 4
Indications 5
Contraindications 5
Clinical Considerations for Patient Selection 5
Warnings 5
Precautions 6
MRI Information 7
Explant and Disposal 8
Potential Adverse Events 8
Instructions for Use 9
Personnel Training 9
Accessories 9
Package Inspection 9
Package Contents 9
Sterilization 9
Pre and Post Procedure Antiplatelet Regimen 10
Implantation Procedure 10
Hospital Electronics System Setup 10
Right Heart Catheterization and Sensor Implant Procedure 11
Patient Identification Card 12
Patient Counseling Information 12
Clinical Study Information 13
Introduction 13
Purpose 14
Methods 13
Patient Demographics and Disposition 14
Primary and Secondary Endpoint Results 15
Primary Safety Endpoints 15
Primary Efficacy Endpoint 16
Secondary Endpoints 16
Medical Management 17
Results from the Entire Randomized Access Period 17
HF Hospitalizations 17
Mortality 17
Freedom from Death or First HF Hospitalization 17
All Cause Hospitalizations 17
Death or All Cause Hospitalizations 18
Results from the Open Access Period (Longitudinal Analysis) 18
Treatment Effects in Women 18
Adverse Events 21
FCC Statement 31
Technical Support 31
3

Description
The CardioMEMSTM HF System provides pulmonary artery (PA) hemodynamic data used
for the monitoring and management of heart failure (HF) patients. The system measures
changes in PA pressure which physicians use to initiate or modify heart failure treatment.
The system includes the following components:
•Implantable wireless sensor with delivery catheter
•Patient or hospital electronics system
•Patient database
The wireless sensor is designed for permanent implantation into the distal pulmonary
artery. Once implanted, the CardioMEMS PA Sensor provides non-invasive hemodynamic
data that is collected in the physician’s office, clinic, hospital, or patient’s home. The data
provided by the system includes:
•PA pressure waveform
•Systolic, Diastolic, and Mean PA pressure
•Heart Rate
This hemodynamic data is transmitted to a secure website that serves as the patient
database so that PA monitoring information is available at all times through the internet.
Changes in PA pressure can be used in conjunction with heart failure signs and
symptoms to guide adjustments to medications.
For information on the operation of the CardioMEMS HF System, please refer to the
System Guide. For information on operation of the patient database, please refer to the
Merlin.netTM Patient Care Network Heart Failure Management Application Help Manual.
For clinical study information, please refer to page 14 of this guide.
Figure 1. PA Sensor
Figure 2. PA sensor and delivery system
4

Table 1. Device model numbers
Device
Model number
PA Sensor and Delivery System
CM2000
Patient Electronics System (landline)
CM1010
Patient Electronics System (GSM)
CM1000
Hospital Electronics System
CM3000
Indications
The CardioMEMS HF System is indicated for wirelessly measuring and monitoring
pulmonary artery (PA) pressure and heart rate in New York Heart Association (NYHA)
Class III heart failure patients who have been hospitalized for heart failure in the previous
year. The hemodynamic data are used by physicians for heart failure management and
with the goal of reducing heart failure hospitalizations.
Contraindications
The CardioMEMS HF System is contraindicated for patients with an inability to take dual
antiplatelet or anticoagulants for one month post implant.
Clinical Considerations for Patient Selection
The following patients may not be appropriate for implantation of the CardioMEMS HF
System:
•Patients with an active infection.
•Patients with a history of recurrent (> 1) pulmonary embolism or deep vein thrombosis
•Patients unable to tolerate a right heart catheterization.
•Patients with a Glomerular Filtration Rate (GFR) <25 ml/min who are non-responsive
to diuretic therapy or who are on chronic renal dialysis.
•Patients with congenital heart disease or mechanical right heart valve(s)
•Patients with known coagulation disorders.
•Patients with a hypersensitivity or allergy to aspirin, and/or clopidogrel.
•Patients who have undergone implantation of a Cardiac Resynchronization Device
(CRT) within the past 3 months.
•If the patient’s BMI is greater than 35, measure the patient’s chest circumference at
the axillary level. If the chest circumference is > 165cm, sensor implantation should
not occur.
Warnings
Before use of the system, read and understand the instructions for use contained in this
manual and in the System Guide.
•Read this manual thoroughly before using the system to avoid potential patient injury
or death.
•Only trained personnel should use this product.
•The implant procedure must be performed by personnel with the appropriate clinical
skills and infrastructure to support right heart catheterizations and endovascular
device placement and deployment over a guidewire.
•The PA Sensor and Delivery System is for single use only. Do not reuse, reprocess,
or resterilize. Reuse, reprocessing, or resterilization may compromise the structural
integrity of the device and/or lead to device failure which, in turn, may result in patient
injury, illness, or death. Reuse, reprocessing, or resterilization may also create a risk
5

of contamination of the device and/or cause patient infection or cross-infection,
including, but not limited to, the transmission of infectious disease(s) from one patient
to another. Contamination of the device may lead to injury, illness, or death of the
patient.
•The implant procedure must be performed under fluoroscopic guidance.
•Do not use a guidewire with a preformed J-shaped tip for sensor delivery. The
preformed J-shaped tip may pull the sensor proximally during guidewire retraction.
•The patient’s PA vessel inner diameter must be > 7mm at the site of device implant.
•Following device implantation, all subsequent right heart catheterizations must be
performed under fluoroscopic guidance. Without fluoroscopy, there could be
inadvertent entanglement between the pulmonary artery catheter and the device.
Precautions
•Only authorized personnel should use this device.
•The delivery system should only be used with a guidewire. Do not aspirate or infuse
through the delivery system guidewire lumen during use.
•Follow standard procedure for catheterization of patients receiving anti-coagulation
therapy. An INR of <1.5 is recommended prior to RHC (Right Heart Catheterization)
and implant if on anticoagulant therapy.
•Protect the sensor from surface contamination once removed from the sterile
package. Ensure that either talc-less gloves are used for the implantation procedure
or rinse all talc from the gloves with sterile saline prior to handling.
•If the hub detaches from the catheter during removal, retract the catheter by holding
the shaft.
•Accuracy of the CardioMEMS HF System is affected by a change in body temperature
(-1mm Hg/ΔºC).
•Accuracy of the CardioMEMS HF System is slightly affected by large changes in
elevation between the initial baseline calibration and subsequent measurements.
(+2mm Hg / 305 meters elevation change).
•An accurate right heart catheterization is required to set system baseline (mean
pressure).
•If a patient has a sensor implanted and another member of the same household is
scheduled to have a sensor implanted, contact Technical Support prior to the second
patient’s implant procedure.
•The mean pressure measurement accuracy of the system may be affected by various
factors. Mean pressure measurement error has been observed when the sensor was
deployed in a vessel which had an inner diameter of less than 7 mm, and in cases
where there was an acute bend in the vessel of >30 degrees at the location of the
sensor. Signs of mean pressure measurement error include the following:
oGradual mean pressure changes without a corresponding proportional change
in the pulse pressure (systolic-diastolic pressure)
oNegative mean pressures
If either feature is observed, temporarily suspend use of the pressure information for
management of the patient and contact Technical Support for further assistance. A
right heart catheterization may be needed to recalibrate the Baseline (mean pressure)
in order to continue use of the system.
•Patients who are currently on chronic anticoagulant therapy should restart treatment
after sensor implantation. Patients who are not currently being treated with chronic
anticoagulant therapy should be placed on aspirin (81 mg or 325 mg) and clopidogrel
(75 mg) daily for one month following the procedure. After one month, the patient
should continue aspirin therapy.
6

•Patients with a reduced ejection fraction should be on stable AHA/ACC guidelines
based medical therapy prior to implant.
•The PA Sensor is a permanent implant. The sensor does not have any batteries that
require replacement or any components that will wear or fail over time. Removal after
implantation is not recommended. No circumstances where the sensor needs to be
removed have been identified and no sensor has been removed during the clinical
trial of the device. The sensor should be retrieved by using standard intra-vascular
and surgical procedures as would be used for other vascular implants if required.
•If there is evidence of a change in device performance, contact Technical Support for
additional information.
•PA Sensor function is unaffected after temporary exposure up to 2 Atmospheres
Absolute (ATA) pressure. Follow the contact process under Technical Support for
additional information if the patient will have hyperbaric chamber exposure or is
planning to scuba dive.
•Pacemakers, ICD’s, and Ventricular Assist Devices (VAD) can work in conjunction
with the PA Sensor and will not affect the performance of the system. Several medical
procedures can also be performed while the sensor is implanted if precaution is taken
to avoid direct contact with the sensor. These procedures include radiofrequency
ablation, ionizing radiation, and diagnostic ultrasound. The effects of therapeutic
ultrasound have not been determined. If therapeutic ultrasound is required, avoid
contact with the sensor.
MRI Information
Non-clinical testing demonstrated that the sensor is MR Conditional. A patient with this
device can be scanned safely, immediately after implantation under the following
conditions:
oStatic magnetic field of 1.5 or 3.0 Tesla
oMaximum spatial gradient magnetic field of 720-Gauss/cm (7200-mT/m) or less
In non-clinical testing, the CardioMEMS PA Sensor produced the temperatures in the
table below during MRI performed for 15 minutes of scanning (per pulse sequence) in the
1.5-Tesla/64-MHz 1and 3-Telsa/128-MHz 2MR systems. These temperature changes will
not pose a hazard to the patient under the conditions indicated.
Table 2. MRI Related Heating
1.5-Tesla
3-Tesla
MR system reported whole body averaged SAR
2.9-W/kg
2.9-W/kg
Calorimetry measured values, whole body averaged SAR
2.1-W/kg
2.7-W/kg
Highest temperature change
1.9°C
2.3°C
MR image quality may be compromised if the area of interest is in the same area or
relatively close to the position of the sensor. Selecting optimal MR imaging parameters to
compensate for the presence of the sensor may be necessary. The maximum artifact size
(as seen on the gradient echo pulse sequence) extends approximately 5 mm relative to
the size and shape of the sensor.
1Magnetom, Siemens Medical Solutions, Malvern, PA. Software Numaris/4, Version Syngo MR
2002B DHHS Active-shielded, horizontal field scanner
2Excite, HDx, Software 14X.M5, General Electric Healthcare, Milwaukee, WI
7

Table 3. Artifact Information
Pulse sequence
T1-SE
T1-SE
GRE
GRE
Signal void size
305-mm2
34-mm2
645-mm2
101-mm2
Plane orientation
Parallel
Perpendicular
Parallel
Perpendicular
Explant and Disposal
The sensor does not require removal before cremation. Do not implant an explanted
sensor in another patient as sterility, functionality, and reliability cannot be ensured.
Potential Adverse Events
Potential adverse events associated with the implantation procedure include, but are not
limited to the following:
•Infection
oUpper respiratory infection
oBronchitis
oPneumonia
oAcute Bronchitis
oGroin abscess
oMethicilin-resistant staphylococcal aureus infection
oPulmonary Infiltration
oSepsis
•Arrhythmias
oVentricular tachycardia
oAtrial fibrillation
oVentricular arrhythmia
oVentricular fibrillation
oAtrial fibrillation with rapid ventricular response
oAtrial flutter
oCardiac dysrhythmias
oTachycardia
oWide complex tachycardia
•Bleeding
oEpistaxis
oHemoptysis
oGI bleed
oBleeding
oBlood in stool
oCatheter site bleeding
oCatheter site ecchymosis
oHematuria
oNose bleeds
•Hematoma
oHematoma
oCatheter site hematoma
oVessel puncture site hematoma
•Thrombus
oArterial thrombosis (limbs)
oBlood clot
•Myocardial infarction
•Transient ischemic attack
•Stroke
•Death
8

•Device embolization
Instructions for Use
Personnel Training
Implanting physicians are required to have successfully completed additional training in
the use of the PA Sensor and Delivery System prior to implant.
Accessories
The accessories required to implant the device and set the sensor’s PA pressure baseline
are listed in the following table. These accessories are not packaged with the device.
Table 4. Accessories
Item
Specifications
Vascular Access Kit
12 Fr Introducer sheath and dilators with access guidewire
PA Catheter
110 cm length
Sensor Delivery
Guidewire
0.018” x 260-300 cm fixed core guidewire with straight or
angled tip (no J-tip)
In addition to the specified accessories, the following catheter lab equipment and supplies
are required to implant and set the sensor’s PA pressure baseline:
•Fluoroscope with digital angiography capabilities and ability to record and recall
images (C-arm or fixed)
•Blood pressure monitoring equipment for a right heart catheterization procedure
•Saline solution
•Radiopaque contrast media
Package Inspection
Inspect the package carefully before opening and check the Use By date on the product
label. Implant of the sensor is not recommended after its expiration date. If the integrity of
the sterile package has been compromised, or the product or package is defective, do not
use the product and contact Technical Support.
Package Contents
The sensor is packaged separately and supplied sterile. Packages contain:
•1 PA Sensor and Delivery System
•1 USB flash drive
•1 temporary patient implant card
•Product documentation
Sterilization
The package contents have been sterilized with ethylene oxide before shipment. The
system is for single use and is not intended to be resterilized. If the sterile package has
been compromised, contact Technical Support.
9

Pre and Post Procedure Antiplatelet Regimen
Patients who are currently on anticoagulant therapy, or those in which chronic
anticoagulant therapy is indicated for heart failure treatment, will restart treatment after
sensor implantation. An INR of <1.5 is recommended prior to sensor implant for patients
who were previously on anticoagulant therapy. Patients should discontinue use of
anticoagulant therapy 1-2 days prior to sensor placement. The standard of care as bridge
therapy to sensor placement should be used in patients who were on anticoagulant
therapy.
Patients who are not being treated with chronic anticoagulant therapy should be placed
on aspirin (81 mg or 325 mg) and clopidogrel (75 mg) daily for one month following
sensor placement. After one month, the patient should continue with aspirin therapy only.
It is important to resume or initiate antiplatelet or anticoagulant therapy following sensor
implantation to reduce the likelihood of thrombotic events.
For patients at risk for gastrointestinal bleeding during the period in which dual antiplatelet
therapy is given, the physician should consider a proton pump inhibitor. Patients at risk
include the elderly or those with a history of gastroduodenal ulcers, GERD, esophagitis,
intestinal polyps or cancer. Patients who smoke or who are using steroids or non-
steroidal anti-inflammatory drugs may also be at risk.
Implantation Procedure
Hospital Electronics System Setup
To set up the Hospital Electronics System:
1. Mount the external system on an IV pole.
2. Position the IV pole near the head of the patient and on the same side as the implant
site.
3. Plug the power cord into a wall outlet.
4. Insert the USB flash drive that came with the PA Sensor and Deliver System.
5. Turn on the power to the system.
6. Select New Implant.
7. Either select or enter the patient information.
8. Confirm that the sensor serial number displayed on the screen matches the number
on the sensor product.
9. Place the right and left ECG electrodes high on the shoulders, and place the
reference electrode below the chest. The leads should be routed away from the chest.
ECG leads draped near the antenna or antenna cable can reduce sensor signal
strength.
10

Right Heart Catheterization and Sensor Implant Procedure
1. Gain percutaneous access to the left or right femoral vein.
2. Introduce 12Fr introducer sheath over a 0.035mm guidewire.
3. Remove the dilator and guidewire.
4. Insert and advance the pulmonary artery (PA) catheter, with balloon inflated, until it
reaches a wedge position in the lower lobe region of the left or right pulmonary artery.
5. Measure PA and PA wedge pressure.
6. Measure cardiac output (optional).
7. Identify target implant site by angiogram through the PA catheter distal lumen (5cc
hand injection of radiographic contrast) with the balloon inflated. Care should be taken
to verify balloon location and lack of over-wedging prior to contrast injection. Target
implant site criteria:
- Target implant vessel is within the lower lobe of either lung and the vessel is
directed towards the feet and back.
- Vessel diameter is > 7 mm and has < 30 degree angulation where body of Sensor
will be placed.
- Vessel diameter is 5 - 8 mm where the distal loop of Sensor will be placed.
- See figure 3.
Figure 3. Target implant site
8. Insert the sensor delivery guidewire through the PA catheter, across the target implant
site.
9. Retract and remove the PA catheter while maintaining the guidewire position.
10. Remove the sensor from the package and flush the guidewire lumen with saline.
11. Carefully swirl the distal end of the catheter (at least 20 cm from the tip) in a bowl of
saline to activate the hydrophilic coating.
12. Introduce the sensor delivery catheter over the guidewire through the sheath and into
the deployment position at the target implant site.
13. Release the sensor: Unscrew the cap on the delivery catheter hub, then retract and
remove the wires from the catheter.
11

14. Under fluoroscopic monitoring, slowly and gently retract and remove the delivery
catheter while maintaining guidewire and sensor position. If resistance is encountered,
do not forcibly retract the hub or catheter shaft.
15. Insert the PA catheter over the guidewire into the main PA.
16. Slowly remove the guidewire while maintaining sensor position.
17. Position the PA catheter tip approximately 5-10 cm proximal to the sensor or within
the opposite lung and measure PA pressure.
18. Acquire the sensor signal using the Hospital Electronics System antenna placed
under the patient’s back, centered under the sensor position.
19. Set Mean PA Pressure Baseline: Once a valid PA pressure waveform is observed on
both the PA catheter and Hospital Electronics System displays, press the “Set
Pressure Baseline” button on the Hospital Electronics System. Enter the mean PA
pressure value measured by the PA catheter.
20. Set Cardiac Output Baseline: Press the “Set CO Baseline” button on the Hospital
Electronics System. Enter the Cardiac Output value which was measured by the PA
catheter. (Optional)
21. Press the “Take Reading” button to capture baseline reading(s).
22. Remove antenna from under patient’s back.
23. Remove pulmonary artery catheter and introducer sheath.
24. Close venous access site per standard of care.
Patient Identification Card
A temporary patient identification card is provided in the device packaging and should be
given to the patient after implantation. Advise patients to keep this card in their
possession at all times. A permanent card will be mailed to the patient within a few weeks
after discharge.
Patient Counseling Information
Discuss these topics with patients prior to discharge:
•Signs and symptoms of infection
•Reporting symptoms
•EMI and RF Interference
12

Clinical Study Information
Introduction
Heart failure (HF) is a major public health problem in the United States affecting over 5
million people with over 1 million HF hospitalizations per year. Elevated pulmonary artery
(PA) pressures may occur prior to signs and symptoms of HF decompensation and can
provide a sound physiologic basis for HF patient management.
The CardioMEMS HF System provides a novel method for measuring PA pressure using
a wireless pressure sensor implanted into the PA, an external communication device, and
a patient database. The CardioMEMS HF System provides physicians knowledge of PA
pressure while the patient is at home allowing them to manage patients proactively with
the goal of reducing heart failure hospitalizations.
The CHAMPION (CardioMEMS HF Sensor Allows Monitoring of Pressures to Improve
Outcomes in NYHA Functional Class III Heart Failure Patients) clinical trial was a
prospective, multicenter, single-blind, randomized, clinical trial in 550 patients across 64
centers in the United States.
Purpose
The goal of the CHAMPION clinical trial was to determine if physicians could reduce HF
hospitalizations by managing patient PA pressures using the CardioMEMS HF System.
Methods
Study Design
550 patients with NYHA Class III HF and a prior HF hospitalization within 12 months were
randomized to standard of care plus the CardioMEMS HF System (Treatment group; 270
patients) or to standard of care only (Control group; 280 patients). All patients were
implanted with the PA Sensor and took daily readings from home. Patients were enrolled
regardless of their baseline ejection fraction so that patients with both reduced and
preserved systolic function were included. Physicians had access to pulmonary artery
pressure information for patients in the Treatment group but not for patients in the Control
group.
Following the completion of Randomized Access, patients transitioned to a period of
Open Access, during which PA pressures were provided to physicians for patients in both
the Treatment and the Control groups. Specifically, physicians continued to have access
to the Treatment group’s PA pressures in an unchanged manner, whereas access to the
Control group’s PA pressure was provided for the first time.
Follow-Up Schedule
After right heart catheterization (RHC) and sensor implantation, all patients had follow-up
study visits at 1 month, 3 months, 6 months, and every 6 months thereafter until study
termination.
13

Study Endpoints
The primary and secondary endpoints were evaluated after 6 months of patient follow-up.
The primary safety endpoints were 1) Freedom from device / system-related
complications (DSRC), and 2) Freedom from pressure sensor failures. The primary
efficacy endpoint was the rate of HF hospitalizations. All hospitalizations were
adjudicated by an independent Clinical Events Committee (CEC) who were blinded to
treatment assignment. Secondary endpoints were tested in a hierarchical fashion and
included changes in PA pressures, proportion of subjects hospitalized for HF, days alive
outside of the hospital for HF, and quality of life. Because blinded follow-up continued
until the last patient completed 6 months of follow-up, the average patient follow-up was
much longer (17.6 months) and pre-specified supplementary analyses were conducted on
the full duration of follow-up data (Randomized Access).
Patient Demographics and Disposition
575 patients were consented for trial enrollment and underwent right heart catheterization.
Of these 575 patients, 25 (4.3%) underwent a right heart catheterization but did not
receive an implant primarily because of anatomical/physiological conditions identified
during the RHC. Of the 550 randomized patients, 270 were assigned to the Treatment
group and 280 to the Control group. The two groups were similar with respect to baseline
characteristics (Table 5).
Table 5. Patient Demographics
Randomized Group
Variables
Treatment
(N=270)
Control
(N=280)
p-value
[1]
Age (years)
61.3 ± 12.98 (270)
61.8 ± 12.73 (280)
0.5927
Male
194/270 (71.9%)
205/280 (73.2%)
0.7745
Race (White)
196/270 (72.6%)
205/280 (73.2%)
0.9236
Systolic BP (mmHg)
121.2 ± 22.52 (270)
123.2 ± 21.01 (280)
0.1286
Heart Rate (bpm)
72.4 ± 12.91 (269)
73.0 ± 12.14 (280)
0.4873
BMI
30.5 ± 6.50 (270)
30.9 ± 7.35 (280)
0.6228
BUN (mg/dL)
29.6 ± 17.99 (248)
28.1 ± 16.17 (267)
0.6325
Creatinine (mg/dL)
1.4 ± 0.47 (270)
1.4 ± 0.42 (280)
0.5560
GFR (mL/min/1.73m²)
60.4 ± 22.50 (270)
61.8 ± 23.20 (280)
0.5638
Ejection Fraction (EF>=40%)
62/270 (23.0%)
57/279 (20.4%)
0.5343
Cardiac Output (L/min)
4.5 ± 1.41 (270)
4.6 ± 1.54 (278)
0.5499
Cardiac Index (L/min/m²)
2.1 ± 0.59 (270)
2.2 ± 0.64 (278)
0.4405
PVR
2.9 ± 2.02 (270)
2.7 ± 1.82 (278)
0.4609
PA Wedge Pressure (mmHg)
17.5 ± 7.97 (270)
19.0 ± 8.12 (280)
0.0276
PA Mean Pressure (mmHg)
28.9 ± 9.92 (270)
29.9 ± 10.05 (280)
0.3021
CRT-D/ICD Implant
179/270 (66.3%)
197/280 (70.4%)
0.3145
Ischemic Cardiomyopathy
158/270 (58.5%)
174/280 (62.1%)
0.4327
Hypertension
207/270 (76.7%)
220/280 (78.6%)
0.6100
Hyperlipidemia
204/270 (75.6%)
218/280 (77.9%)
0.5458
Coronary Artery Disease
182/270 (67.4%)
202/280 (72.1%)
0.2290
History of MI
134/270 (49.6%)
137/280 (48.9%)
0.9320
Diabetes Mellitus
130/270 (48.1%)
139/280 (49.6%)
0.7337
AFIB
120/270 (44.4%)
135/280 (48.2%)
0.3932
COPD
76/270 (28.1%)
83/280 (29.6%)
0.7078
ACE/ARB use
205/270 (75.9%)
222/280 (79.3%)
0.3584
Beta Blocker use
243/270 (90.0%)
256/280 (91.4%)
0.6595
[1] Wilcoxon Rank-Sum Test for continuous measures and Fisher's exact test for categorical measures.
14

The mean follow-up during Randomized Access was 17.6 months for a total duration of
approximately 800 patient years. During the course of Randomized Access, 93 patients
in the Treatment group and 110 patients in the Control group exited the study with the
primary reason being death.
A total of 347 patients (177 in the Treatment group and 170 in the Control group)
completed Randomized Access and entered Open Access. The mean follow-up during
Open Access was 13 months for a total duration of approximately 400 patient years.
During the course of Open Access, 58 patients in the Treatment group and 43 patients in
the Control group exited the study with the primary reason being death.
Primary and Secondary Endpoint Results
Primary Safety Endpoints
The CHAMPION clinical trial met the two primary safety endpoints: (1) Freedom from
device/system related complications (DSRC) and (2) Freedom from sensor failure. The
protocol pre-specified objective performance criteria (OPC) were that at least 80% of
patients were to be free from DSRC and at least 90% were to be free from pressure
sensor failure. Of the 575 patients in the safety population, 567 (98.6%) were free from
DSRC at 6 months (lower confidence limit 97.3%, p<0.0001). This lower limit of 97.3% is
greater than the pre-specified OPC of 80% (Table 6a and 6b). There were no sensor
explants or repeat implants and all sensors were operational at 6 months for a freedom
from sensor failure of 100% (lower confidence limit 99.3%, p<0.0001). This lower limit of
99.3% is greater than the pre-specified OPC of 90% (Table 7).
Table 6a. Primary Safety Endpoint – Freedom from Device/System Related Complications
Device/System Related
Complications (n=575)
Lower 95.2%
Confidence
Limit
2
Objective Performance
Criterion (OPC) p-value3
Yes
No
8 (1.4%)1
567 (98.6%)
97.3%
80%
p<0.0001
1 DSRCs (8 total) by group: Consented but not randomized (2), Treatment (3), Control (3)
2Exact 95.2% Clopper-Pearson lower confidence limit
3
p-value from exact test of binomial proportions compared to 80% for all patients
Table 6b. Primary Safety Endpoint – Description of Device/System Related Complications
Description
Number of Subjects with Device or System
related complication (%) (N = 575)
Hemoptysis
1 (0.2%)
Sensor did not deploy
1 (0.2%)
Transient Ischemic Attack (TIA)
1 (0.2%)
Atypical chest pain
1 (0.2%)
Sepsis → death
1 (0.2%)
Atrial arrhythmia → death
1 (0.2%)
Arterial embolism (upper extremity)
1 (0.2%)
Pulmonary artery (in-situ) thrombus
1 (0.2%)
Total Subjects Experiencing a DSRC
8 (1.4%[1], 95.2% LCB 97.3%)
15

Table 7. Primary Safety Endpoint – Freedom from Pressure Sensor Failures
Pressure Sensor
Failures (n=550)
Lower 95.2%
Confidence
Limit
2
Objective Performance
Criterion (OPC) p-value3
Yes
No
0 (0.0%)
550 (100%)1
99.3%
90%
p<0.0001
1Pressure sensor failure counts by group: Treatment (0), Control (0)
2Exact 95.2% Clopper-Pearson lower confidence limit
3
p-value from exact test of binomial proportions compared to 90% for all patients
Primary Efficacy Endpoint
The primary efficacy endpoint of the CHAMPION clinical trial was the rate of HF
hospitalizations during the first 6 months of Randomized Access. There were 84 HF
hospitalizations in the Treatment group compared with 120 HF hospitalizations in the
Control group. This difference between the groups represented a 28% reduction in the 6-
month rate of HF hospitalization in the Treatment group (0.32 hospitalizations per patient
in the Treatment group vs. 0.44 hospitalizations per patient in the Control group, HR 0.72,
95% CI 0.60-0.85, p = 0.0002) (Table 8).
Table 8. Primary Efficacy Endpoint – HF Hospitalization rates During First 6 months of Randomized
Access
Number of
HF Hospitalizations 6 Month HF Hospitalization Rate
Hazard Ratio
(95% CI)
[p-value]
1
Treatment Group
(n=270)
84 0.32 0.72
(0.60-0.85)
p=0.0002
Control Group
(n=280)
120 0.44
1p-value and hazard ratio from negative binomial regression model
Secondary Endpoints
The four secondary efficacy endpoints were analyzed hierarchically at 6 months (Table 9).
At baseline, both Treatment and Control patients had similar PA mean pressures. When
compared with patients in the Control group, the patients in the Treatment group had
greater reduction in mean PA pressure (p=0.0077); were less likely to be hospitalized for
heart failure (p=0.0292); spent more days alive outside of the hospital for heart failure
(p=0.0280); and reported a better quality of life (Minnesota Living with Heart Failure
Questionnaire) (p=0.0236).
Table 9. Secondary Efficacy Endpoints at 6 Months
Treatment
Control
p-value
Change from baseline in mean pulmonary artery
pressure, area under the curve (mean mmHg
-
days)
-155.7
(n=265) 0.32 0.00771
Proportion of patients hospitalized for heart failure
(%)
55 (20.4%)
(n=270)
80 (28.6%) 0.02922
Days alive outside the hospital for heart failure
(mean)
174.4
(n=270)
172.1
(n=280)
0.02803
Minnesota Living with Heart Failure Questionnaire
(mean[median])
45.2 [45.0]
(n=229)
50.6 [52.0]
(n=236)
0.02364
1 p-value from analysis of covariance with baseline pressure as the covariate
2 p
-value from Fisher's exact test
3 p
-value fromWilcoxon rank sum test after controlling for subject duration in study (i.e., days alive outside the hospital /
subject duration x 180)
4 p-value from two-group t-test
16

Medical Management
Physicians responded to Treatment patients’ elevated PA pressures by making
medication changes to lower PA pressures in an attempt to reduce the risk for HF
hospitalization. Physicians documented all medication changes for all patients and
indicated whether the change was made in response to PA pressures or standard of care
information. During the 6-month follow-up period, physicians made 1113 HF medication
changes in the Treatment group and 1061 HF medication changes in the Control group in
response to standard of care information. In the Treatment group only, physicians made
1404 HF medication changes in response to PA pressures, primarily through diuretics and
vasodilators. This incremental HF management in response to PA pressures using the
CardioMEMS HF System led to a significant reduction in HF hospitalizations.
Results from the Entire Randomized Access Period
HF Hospitalizations
During the entire Randomized Access period, the rate of HF hospitalizations was 33%
lower in the Treatment group than in the Control group (0.46 vs. 0.68 annualized HF
hospitalization rates, HR 0.67, 95%CI 0.55-0.80) (Table 10). The magnitude of the effect
during the entire Randomized Access period was slightly larger than that seen during the
6-month primary endpoint period (33% vs. 28%), indicating durability of the treatment
effect. The number needed to treat (NNT) per year to prevent one HF hospitalization was
4. For every 100 patients treated, 23 HF hospitalizations would be prevented per year.
Table 10. HF Hospitalization Rates During Randomized Access
Number of HF
Hospitalizations Annualized HF Hospitalization Rate Hazard Ratio (95% CI)
NNT Per Year to
Prevent One HF
Hospitalization
Treatment Group
(n=270)
182 0.46 0.67
(0.55-0.80)
4
Control Group
(n=280)
279 0.68
Hazard ratio from Andersen-Gill model.
Mortality
The proportion of patients who died in the Treatment group (18.5%) was smaller than in
the Control Group (22.9%) with a relative risk reduction of 20% (HR 0.80, 95% CI 0.55 –
1.15).
Freedom from Death or First HF Hospitalization
The proportion of patients who died or had at least one HF hospitalization in the
Treatment group (44.8%) was smaller than in the Control Group (51.8%) with a relative
risk reduction of 23% (HR 0.77, 95% CI 0.60 – 0.98).
All Cause Hospitalizations
All cause hospitalizations were reduced in the Treatment group (554 in the Treatment
group vs. 672 in the Control group, HR 0.84, 95% CI 0.75 – 0.95). The NNT per year to
prevent one all cause hospitalization was 4. For every 100 patients treated, 26 all cause
hospitalizations would be prevented per year.
17

Death or All Cause Hospitalizations
Death or all cause hospitalizations were reduced in the Treatment group (604 in the
Treatment group vs. 736 in the Control group, HR 0.84, 95% CI 0.76 – 0.94). The NNT
per year to prevent one death or all cause hospitalization was 4. For every 100 patients
treated, 29 deaths or all cause hospitalizations would be prevented per year.
Results from the Open Access Period (Longitudinal Analysis)
In the Open Access period, physicians were given access to PA pressures in the Control
group for the first time while access to PA pressures for the Treatment group continued.
In the Control group (n=170), new physician access to PA pressures resulted in a 48%
reduction in HF hospitalization rates (0.36 vs. 0.68, HR 0.52, 95% CI 0.40-0.69,
p<0.0001*). In the Treatment group (n=177), continued physician access to PA pressures
resulted in the maintenance of low HF hospitalization rates (0.45 vs. 0.48, HR 0.93, 95%
CI 0.70-1.22, p=0.5838*).
To account for potential longitudinal confounders, the change in HF hospitalization rates
in the Control group as result of new access to PA pressures was compared to the
change in HF hospitalization rates in the Treatment group. The change in HF
hospitalization rates in the Control group was significantly greater than in the Treatment
group (HR 0.56, 95% CI 0.38-0.83, p=0.0040*), indicating that the significant 48%
reduction in HF hospitalization rates observed in the Control group was the result of
physician access to PA pressure and not longitudinal effects.
(*P-values should be interpreted with caution because the analyses including Part 2 data were not
specified before the onset of the study and there are various sources of confounding effects which
cannot be separated from the treatment effect.)
Treatment Effects in Women
The CHAMPION study was not powered to show statistical significance for gender, thus a
complete determination of the effect of the device in women cannot be made. At the
request of FDA, a post-hoc gender analysis was conducted for the CHAMPION study,
and the initial finding of a treatment-by-gender interaction for the effect of the
CardioMEMS device on the HF hospitalization rate was related to (1) fewer women being
in the study and the short duration of follow-up leading to a small number of events in
women; and (2) the low HF hospitalization rate in Control women due to an early excess
of deaths in women in the Control group, which acted as a competing risk to censor the
occurrence of hospitalizations for heart failure.
A further analysis of the treatment-by- gender interaction was performed over the full
period of Randomized Access and by incorporating death in the Cox Proportional
Hazards. When these limitations and confounding issues were evaluated over the full
period, there was neither a qualitative nor quantitative treatment-by-gender interaction
and the treatment effect remained positive, independent of gender. However, the
analyses conducted do not alleviate the possibility of a diminished treatment effect in
women. Given the small number of women enrolled and small number of events observed
in women, the true treatment effect in this group remains uncertain. In order to further
complement and evaluate the results obtained during the CHAMPION study, the effect of
the device in women is being studied as part of the post approval study.
The figures below depict the Freedom from HF Hospitalization and Freedom from Death
for Men and Women over the Full Randomized Period (Part 1). Figure 6 below depicts the
composite endpoint of Freedom from HF Hospitalization or Death for Men and Women
18

over the Full Randomized Period (Part 1). They illustrate the apparent difference in
treatment effect by gender. As seen in Figure 4, for HF hospitalizations alone, treatment
and control women have similar outcomes. However, as seen in Figure 5, control women
had an increased early mortality creating a competing risk for HF hospitalizations i.e.,
fewer control women were alive to have HF hospitalizations. Figure 6 examines Freedom
from HF Hospitalization or Death and indicates a non-significant trend favoring women in
the treatment group.
Figure 4. Freedom from HF Hospitalization over the Full Randomized Period (Part 1).
Figure 5. Freedom from Death over the Full Randomized Period (Part 1).
Figure 6. Freedom from HF Hospitalization or Death over the Full Randomized Period (Part 1).
19

Also performed were an Anderson-Gill Model with Frailty, Anderson Gill Model with
Robust Sandwich Estimates (RSE) and Negative Binomial Regression using an endpoint
of time to HF hospitalization or death in Part 1 and Part 1 + Part 2. As seen in the gray
rows in Tables 11 and 12 below, all the competing risk analyses taking death into account
as a competing risk show that there was no evidence of a treatment-by-gender interaction
if a p-value of 0.05 is used. However, when analyses for interaction by gender are
conducted, a p-value of 0.15 is typically used because the analysis is typically not
powered appropriately. When considering a p-value of 0.15, there was some evidence of
treatment-by-gender interaction in the competing risk analyses under the following
models:
•AG Model with Frailty for Part 1
•NB Regression for Part 1
•AG Model with Robust Sandwich Estimate for Part 1 + Part 2
•GEE NB Regression for Part 1 + Part 2
Table 11. Results of treatment by gender interaction using different statistical models
Models
Estimate
SE
p-value
Part 1
Cox Model: Endpoint of first HFR hospitalization or Death
-0.113
0.289
0.6968
Cox Model: Endpoint of first HFR hospitalization
-0.330
0.327
0.3131
AG Model with Frailty: Endpoint of HFR hospitalization or Death
-0.373
0.239
0.1211
AG Model with Frailty: Endpoint of HFR hospitalization
-0.531
0.262
0.0459
AG Model with RSE: Endpoint of HFR hospitalization or Death
-0.433
0.316
0.1712
AG Model with RSE: Endpoint of HFR hospitalization
-0.577
0.360
0.1094
NB Regression: Endpoint of HFR hospitalization or Death
-0.412
0.242
0.0896
NB Regression: Endpoint of HFR hospitalization
-0.573
0.191
0.0027
Part 1 + Part 2
Cox Model: Endpoint of first HFR hospitalization or Death
-0.204
0.249
0.4121*
Cox Model: Endpoint of first HFR hospitalization
-0.427
0.284
0.1331*
AG Model with Frailty: Endpoint of HFR hospitalization or Death
-0.376
0.274
0.1697*
AG Model with Frailty: Endpoint of HFR hospitalization
-0.588
0.271
0.0301*
AG Model with RSE: Endpoint of HFR hospitalization or Death
-0.477
0.274
0.0816*
AG Model with RSE: Endpoint of HFR hospitalization
-0.642
0.313
0.0399*
GEE NB Regression: Endpoint of HFR hospitalization or Death
-0.488
0.283
0.0841*
GEE NB Regression: Endpoint of HFR hospitalization
-0.761
0.319
0.0172*
Table 12. The Treatment vs. Control effects by Gender over Part 1 and over Part 1+ Part 2 under
different models
Males
Hazard Ratio
p-value
Part 1 (Treatment vs. Control)
AG Model with Frailty: Endpoint of HFR hospitalization or Death
0.67
0.0007
AG Model with Frailty: Endpoint of HFR hospitalization
0.64
0.0004
Part 1 + Part 2 (Former Control vs. Control)
AG Model with Frailty: Endpoint of HFR hospitalization or Death
0.70
0.0176*
AG Model with Frailty: Endpoint of HFR hospitalization
0.53
<0.0001*
Females
Hazard Ratio
p-value
Part 1 (Treatment vs. Control)
AG Model with Frailty: Endpoint of HFR hospitalization or Death
0.99
0.9440
AG Model with Frailty: Endpoint of HFR hospitalization
1.07
0.7584
Part 1 + Part 2 (Former Control vs. Control)
AG Model with Frailty: Endpoint of HFR hospitalization or Death
0.80
0.4512*
AG Model with Frailty: Endpoint of HFR hospitalization
0.61
0.1482*
(*P-values should be interpreted with caution because the analyses including Part 2 data were not specified before
the onset of the study and there are various sources of confounding effects which cannot be separated from the
treatment effect.)
20