Hemodynamic-GUIDEd Management of Heart Failure
Phase: NA
Conditions: Heart Failure, Heart Failure, Systolic, Heart Failure, Diastolic, Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure NYHA Class IV, Heart Failure，Congestive, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection Fraction, Heart Failure; With Decompensation
Sponsor: Abbott Medical Devices

NCT03387813
Date: 06-FEB-2020

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 2 of 71 
 
 
Table of Contents 
 
1 
Introduction............................................................................................................................................. 5 
2 
Background and Justification for Clinical Trial ....................................................................................... 5 
2.1.1 
CardioMEMS™ Clinical Experience .......................................................................................... 5 
2.1.2 
Patient Selection for CardioMEMS™ Therapy .......................................................................... 6 
2.1.3 
Natriuretic Peptides in HF.......................................................................................................... 6 
2.1.4 
Clinical Trial Rationale ............................................................................................................... 7 
3 
Device(s) Under Investigation ................................................................................................................ 7 
 
Identification and Description of the Devices under Investigation ................................................. 7 
3.1.1 
Identification .............................................................................................................................. 7 
3.1.2 
Device Description and Intended Purpose ................................................................................ 8 
3.1.3 
Intended Purpose within the Clinical Trial ................................................................................. 9 
3.1.4 
Device Handling and Storage .................................................................................................... 9 
4 
Clinical Trial Design ............................................................................................................................... 9 
4.1.1 
Clinical Trial Duration ................................................................................................................ 9 
4.1.2 
GUIDE-HF Randomized Arm .................................................................................................. 10 
4.1.3 
GUIDE-HF Single Arm............................................................................................................. 10 
 
Objectives .................................................................................................................................... 11 
 
Endpoints ..................................................................................................................................... 11 
4.3.1 
GUIDE-HF Randomized Arm .................................................................................................. 11 
4.3.2 
GUIDE-HF Single Arm............................................................................................................. 12 
 
Clinical Trial Population ............................................................................................................... 13 
4.4.1 
Inclusion Criteria ...................................................................................................................... 13 
4.4.2 
Exclusion Criteria ..................................................................................................................... 14 
4.4.3 
Enrollment of Medicare Beneficiaries ...................................................................................... 14 
4.4.4 
Historically Underrepresented Demographic Subgroups ........................................................ 15 
5 
Clinical Trial Procedures ...................................................................................................................... 15 
 
Clinical Trial Flow Chart .............................................................................................................. 16 
 
Subject Recruitment .................................................................................................................... 18 
 
Point of Enrollment ...................................................................................................................... 18 
 
Scheduled Procedures ................................................................................................................ 18 
5.4.1 
Screening Procedures ............................................................................................................. 18 
5.4.2 
Informed Consent .................................................................................................................... 19 
5.4.3 
Baseline Procedures ............................................................................................................... 19 
5.4.4 
Implant Procedure ................................................................................................................... 20 
5.4.5 
Randomization ......................................................................................................................... 21 
5.4.6 
Prior to Discharge .................................................................................................................... 21 
5.4.7 
Hemodynamic Management of HF – Treatment Guidance ..................................................... 21 
5.4.8 
Patient database (Merlin.net™) ............................................................................................... 22 
5.4.9 
PA Pressure Readings in the Hospital .................................................................................... 22 
5.4.10 
Post-Discharge Subject Phone Contact Requirements ...................................................... 23 

 
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Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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5.4.11 
Scheduled Follow- ups ........................................................................................................ 24 
5.4.12 
Data Viewing After 12 Months ............................................................................................. 24 
 
Unscheduled Visits ...................................................................................................................... 24 
 
Healthcare Economic Data Collection ......................................................................................... 25 
 
Description of Activities Performed by Sponsor Representatives ............................................... 25 
 
Subject Clinical Trial Completion ................................................................................................. 25 
 
Subject Withdrawal ...................................................................................................................... 25 
 
Clinical Trial Committees ............................................................................................................. 26 
5.10.1 
Steering Committee ............................................................................................................. 26 
5.10.2 
Publication Committee......................................................................................................... 26 
5.10.3 
Data Safety Monitoring Board (DSMB) ............................................................................... 26 
5.10.4 
CEC ..................................................................................................................................... 26 
6 
Statistical Considerations ..................................................................................................................... 26 
 
GUIDE-HF Randomized Arm ...................................................................................................... 27 
6.1.1 
Primary Endpoint ..................................................................................................................... 27 
6.1.2 
Secondary Endpoints .............................................................................................................. 27 
 
GUIDE-HF Single Arm ................................................................................................................ 29 
6.2.1 
Primary Endpoint ..................................................................................................................... 29 
6.2.2 
Secondary Endpoints .............................................................................................................. 30 
 
Justification of Clinical Trial Design ............................................................................................. 31 
 
Multiplicity .................................................................................................................................... 32 
 
Overall Sample Size .................................................................................................................... 33 
 
Statistical Criteria for Termination ............................................................................................... 33 
 
Deviations from Statistical Plan ................................................................................................... 33 
7 
Risks and Benefits ............................................................................................................................... 33 
 
Risks Associated with the Device under Investigation ................................................................ 33 
7.1.1 
Anticipated AEs ....................................................................................................................... 33 
7.1.2 
Anticipated ADEs/SADEs ........................................................................................................ 34 
7.1.3 
Non-AE Device Issue .............................................................................................................. 35 
 
Risk Control Measures ................................................................................................................ 35 
 
Possible interactions with concomitant treatments ..................................................................... 35 
 
Anticipated Benefits ..................................................................................................................... 35 
 
Risk-to-Benefit Rationale ............................................................................................................. 35 
 
History of Device Modifications or Recall .................................................................................... 36 
8 
Requirements for Investigator Records and Reports ........................................................................... 36 
 
Deviations from CIP..................................................................................................................... 36 
 
Safety Reporting .......................................................................................................................... 36 
8.2.1 
Criteria and Guidelines for Reportable Events ........................................................................ 37 
8.2.2 
Criteria and Guidelines for Non-Reportable Events ................................................................ 38 
8.2.3 
Subject Death .......................................................................................................................... 38 
8.2.4 
UADEs ..................................................................................................................................... 38 
 
Source records ............................................................................................................................ 38 

 
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Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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Records Retention ....................................................................................................................... 39 
9 
Clinical Data Handling .......................................................................................................................... 39 
 
Protection of Personally Identifiable Information ......................................................................... 39 
 
Data Management Plan (DMP) ................................................................................................... 39 
 
Document and Data Control ........................................................................................................ 39 
9.3.1 
Traceability of Documents and Data ....................................................................................... 39 
9.3.2 
Recording Data ........................................................................................................................ 39 
10 Monitoring............................................................................................................................................. 40 
11 Compliance Statement ......................................................................................................................... 40 
 
Statement of Compliance ............................................................................................................ 40 
 
Quality Assurance Audits and Regulatory Inspections ............................................................... 40 
 
Repeated and Serious Non-Compliance ..................................................................................... 40 
12 Suspension or Premature Termination of the Clinical Trial ................................................................. 41 
13 Clinical Trial Conclusion ....................................................................................................................... 41 
14 Publication Policy ................................................................................................................................. 41 
15 Reporting Results on ClincalTrials.gov Website .................................................................................. 42 
Appendix A: CIP Revisions ......................................................................................................................... 43 
Appendix B: Acronyms ................................................................................................................................ 44 
Appendix C: Definitions ............................................................................................................................... 46 
Appendix D: Justification of NT-proBNP and BNP Thresholds ................................................................... 48 
Appendix E: Guidance for Management of Hemodynamic Parameters ..................................................... 51 
Appendix F: Measures to Ensure Enrollment into the Randomized Arm .................................................... 53 
Appendix G: NT-proBNP and BNP Thresholds According to BMI .............................................................. 54 
Appendix H: Body Mass Index Calculator ................................................................................................... 55 
Appendix I: Subject-Reported Outcome Measures ..................................................................................... 56 
Appendix J: Calculation of Glomerular Filtration Rate ................................................................................ 57 
Appendix K: 6-Minute Hall Walk Test Instructions ...................................................................................... 58 
Appendix L: Enrollment Flow Chart ............................................................................................................. 59 
Appendix M: Randomized Arm Subject Contact Worksheet ....................................................................... 60 
Appendix N: Single Arm Echocardiogram and Quality-of-Life Sub-Study .................................................. 62 
Appendix O: CIP Summary ......................................................................................................................... 63 
Appendix P: Bibliography ............................................................................................................................ 69 
 
 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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1 
Introduction 
This document is a clinical investigation plan (CIP) for the Hemodynamic-GUIDEd Management of Heart 
Failure (GUIDE-HF) clinical trial. This clinical trial is intended to demonstrate the effectiveness of the 
CardioMEMS™ HF System in patients with New York Heart Association (NYHA) Class II, III, or IV Heart 
Failure (HF) who have an elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or an elevated 
Brain Natriuretic Peptide (BNP)) and/or a prior HF Hospitalization (HFH). This clinical trial will be 
conducted under an investigational device exemption (IDE) and is intended to support an expanded 
indication for the CardioMEMS™ HF System. This clinical trial is sponsored by Abbott. 
 
The clinical trial will be conducted in accordance with this CIP. All parties involved in the conduct of the 
clinical trial will be qualified by education, training, or experience to perform their tasks, and this training 
will be documented appropriately. 
2 
Background and Justification for Clinical Trial 
HF affects over six million Americans, with 960,000 new cases diagnosed each year. The syndrome 
tends to be progressive and is associated with severe morbidity and high mortality. HF costs the United 
States healthcare system over $30 billion annually (1), with the largest cost component associated with 
over 1.2 million annual hospitalizations required to provide rescue therapy during acute decompensation 
of the chronic condition. HF is a growing pandemic with estimates from the American Heart Association 
(AHA) predicting the prevalence of HF in the United States to approach nine million patients by 2030, with 
an associated increase to three million hospitalizations yearly. Innovative approaches focusing on 
decreasing decompensation events are needed to not only improve patient quality of life and survival, but 
also reduce the overall cost of delivering healthcare to HF patients (1-3). Implantable hemodynamic 
monitoring systems are one such innovative approach that have been proven effective in maintaining 
stability in selected HF patients by providing a novel clinical disease management strategy that 
proactively avoids decompensation, replacing the traditional reactive rescue approach to treat acute 
decompensation. Remote pulmonary artery (PA) pressure monitoring provides clinical providers with 
actionable data to guide patient-centric individualized medication dosing and adjustments with the goal of 
preventing HFHs or other decompensation events (4-7). The CardioMEMS™ HF System is currently the 
only FDA approved system indicated for previously hospitalized NYHA Class III HF patients, regardless of 
left ventricular ejection fraction (LVEF), with the goal of reducing HFHs. The system is comprised of a 
lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA 
pressure measurements from the patient’s home to a secure website. Healthcare professionals are able 
to access these measurements and associated waveforms to remotely guide individualization of medical 
management for their patients with chronic HF. The purpose of the GUIDE-HF clinical trial is to discover 
whether hemodynamic-guided HF management is applicable to a larger group of at-risk HF patients and 
whether maintaining hemodynamic stability improves overall survival and quality-of-life in such HF 
patients. 
2.1.1 
CardioMEMS™ Clinical Experience 
The safety and effectiveness of the CardioMEMS™ HF System was evaluated in the CHAMPION 
(CardioMEMS™ HF Sensor Allows Monitoring of Pressures to Improve Outcomes in NYHA Functional 
Class III HF Patients) trial (ClinicalTrials.gov Identifier: NCT00531661). CHAMPION was a prospective, 
multi-center, randomized, controlled trial, which demonstrated a significant reduction in HFHs when PA 
pressure measured by the CardioMEMS™ PA Sensor was used by clinicians to guide HF patient 
management (Treatment Group), compared to patients managed without clinician knowledge of PA 
pressure information (Control Group) (5, 8). This included the first treatment strategy to successfully 
improve outcomes in HF patients with a preserved ejection fraction (EF) (HFpEF) (9). Additionally, 
hemodynamic-guided HF care in patients with reduced HF (HFrEF) augmented the survival benefit of 
guideline directed medical therapy (GDMT) (10, 11). Results of the CHAMPION trial led to the Food and 
Drug Administration (FDA) approval of the CardioMEMS™ HF System for wirelessly measuring PA 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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pressure to guide HF management in NYHA Class III HF patients who experienced a HFH in the previous 
year.  
 
Early experience with the CardioMEMS™ HF System in a post-FDA approval, real-world environment 
continues to support the utility of hemodynamic-guided HF management for this population. In particular, 
PA pressure-guided HF management using the implantable CardioMEMS™ PA Sensor in large real-
world cohorts demonstrated reduced HFHs (12), along with a concomitant reduction in PA pressure (13). 
Real-world reductions in HFHs were associated with significant cost savings based on Medicare claims 
data. Additional clinical evidence on post-market experience with CardioMEMS™ in this population is 
currently being generated in a post-approval registry study (PAS, NCT02279888) in 1,200 patients 
followed for two years. Enrollment in this registry was completed earlier than expected and is currently in 
the long-term follow-up phase. Preliminary results in the first 300 patients followed for at least six months 
found a lower HFH rate compared to the CHAMPION Trial Treatment Group, despite the fact that the 
PAS population is older with more advanced HF syndromes (14, 15).  
2.1.2 
Patient Selection for CardioMEMS™ Therapy 
The CardioMEMS™ HF System is currently indicated for use in NYHA Class III HF patients, who have a 
documented HFH in the prior year. However, determination of these prerequisite conditions for patient 
selection can be challenging. The NYHA classification of HF symptoms is designed to subjectively 
quantify an individual’s burden of congestive symptoms in order to provide specific medical and device 
interventions appropriate for the patient’s condition. Accurate assessment of NYHA Class is limited by 
several important factors including the tendency for patients to accommodate chronic symptoms and 
variability in healthcare providers’ diligence in historical assessment. These limitations may lead to 
misclassification of HF patient status, leading to a missed opportunity for preventive care. Biomarker 
assessment of HF patient status, particularly utilizing B-Type Natriuretic Proteins (NT-proBNP or BNP) 
may provide a superior means to determine the presence of subclinical congestion, thus providing a 
better prognostic assessment of the patient’s subsequent risk for decompensation than NYHA class. 
Furthermore, it is now clear that United States clinical management trends have shifted away from 
hospitalization to treat acutely decompensated HF (ADHF) to increased reliance on outpatient 
intravenous medication intervention. However, regardless of the venue, decompensation requiring rescue 
therapy is associated with increased long-term mortality risk. Therefore, it is plausible to hypothesize that 
hemodynamic-guided care may be appropriate for patients whose clinical congestion status is determined 
by NT-proBNP (or BNP) even when clinical symptoms are assessed as NYHA Class II, III, or IV HF. 
Given the prognostic value of elevated NT-proBNP (or BNP), patients without history of a previous HFH 
may also benefit from hemodynamic-guided HF management strategies. 
2.1.3 
Natriuretic Peptides in HF 
Natriuretic peptides, specifically NT-proBNP and BNP, are released into the circulation directly from the 
myocardium due to increased end-diastolic wall stress as a result of increased end diastolic volume and 
pressure (16). Natriuretic peptides are most commonly used to support the diagnosis of HF in patients 
with dyspnea, and numerous studies have demonstrated that NT-proBNP and BNP are strong 
independent predictors of adverse clinical outcome in HF patients (17). In the Breathing Not Properly 
study, a BNP threshold of 100 pg/ml accurately diagnosed acute HF with a sensitivity of 90% and a 
specificity of 76% (18). In the COMET study, a progressively increasing risk for mortality was observed 
with every 10% increase in NT-proBNP (19). The Agency for Healthcare Research and Quality of the 
Department of Health and Human Services in 2006 assessed 58 studies where NT-proBNP or BNP were 
evaluated in predicting cardiac events in primarily NYHA Class II, III or IV HF patients (20). A majority of 
the studies found baseline NT-proBNP or BNP to be independent predictors of mortality. This makes NT-
proBNP and/or BNP assessments a promising alternative to prior HFHs for objectively identifying patients 
who are at high risk for HFHs and mortality, and who may derive clinical benefits from PA pressure-
guided HF management (for more details see Appendix D). These data have supported a Class I 
recommendation for measurement of NT-proBNP or BNP to establish prognosis or disease severity in 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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chronic HF (21) and have resulted in NT-proBNP and BNP assessment being included as an entry 
criterion for numerous clinical trials in HF such as LAPTOP-HF (trial of a device for hemodynamic 
monitoring, NCT01121107 (7)), PARADIGM-HF and PARAGON-HF (trials of sacubitril-valsartan in HFrEF 
and HFpEF patients, NCT01035255 (22, 23), NCT01920711 (24)), and COAPT (trial of MitraClip 
percutaneous repair for functional mitral regurgitation, NCT01626079). 
2.1.4 
Clinical Trial Rationale 
These data support the hypothesis that hemodynamic-guided HF management using the CardioMEMS™ 
HF System may be effective in a NYHA Class II, III, or IV HF patient population with elevated NT-proBNP 
(or BNP). Furthermore, the utility of elevated NT-proBNP (or BNP) and its equivalence to a history of 
previous HFHs for appropriate selection of HF patients for CardioMEMS™ implantation is plausible, but 
currently unknown. Hence, the rationale for conducting this clinical trial is two-fold: 
 
• 
To generate scientific evidence supporting the clinical benefit of PA pressure-guided HF 
management in a broad range of HF patients (NYHA Class II, III, or IV), reflecting contemporary 
methods of patient selection (elevated NT-proBNP (or BNP)) 
• 
To demonstrate the equivalence of elevated NT-proBNP (or BNP) to prior HFHs for selecting the 
appropriate candidates who will clinically benefit from PA pressure-guided HF management, and 
to allow for the expansion of the current label to include NYHA Class III HF patients with elevated 
NT-proBNP (or BNP) 
 
This clinical trial proposes to build on the clinical experience gained from the CHAMPION trial and 
attempts to fill an important clinical evidence gap in the management of eligible HF patients (including 
Medicare beneficiaries). The Sponsor is proposing to conduct an IDE trial to obtain pre-market approval 
(PMA) of the CardioMEMS™ HF System for NYHA Class II, III, or IV HF patients who have experienced 
either a HFH within the last 12 months (“prior HFH”) or have elevated NT-proBNP (defined as ≥ 1000 
pg/mL for LVEF ≤ 40% or ≥ 700 pg/mL for LVEF > 40%) (or elevated BNP, defined as ≥ 250 pg/mL for 
LVEF ≤ 40% or ≥175 pg/mL for LVEF > 40%) within the last 30 days. Thresholds for NT-proBNP and 
BNP (for both LVEF ≤ 40% and LVEF > 40%) will be corrected for body mass index (BMI) using a 4% 
reduction per BMI unit over 25 kg/m2 (23), see Appendix G for NT-proBNP (and BNP) thresholds 
according to BMI. 
3 
Device(s) Under Investigation 
 
Identification and Description of the Devices under Investigation 
3.1.1 
Identification 
Table 1 details the devices to be used in this trial. Although market released, the CardioMEMS™ HF 
System is not FDA approved for the proposed clinical trial population (NYHA Class II, III, or IV HF 
patients with elevated NT-proBNP (or BNP)). 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 11 of 71 
 
 
complete baseline assessments. Within 60 days of consent, subjects will receive a CardioMEMS™ HF 
System. Subjects will be considered enrolled in the Single Arm once all entry criteria are met, informed 
consent is provided, and implantation of the CardioMEMS™ PA Sensor is attempted. Safety information 
and adverse events (AEs) will be reported (per section 8.2) for all enrolled subjects. However, subjects 
will only contribute towards the sample size and primary, secondary effectiveness, and descriptive 
endpoint analyses following successful implantation. Subjects will upload PA pressure information daily, 
and receive HF management guided by PA pressure information.  
 
The GUIDE-HF Single Arm will include approximately 2600 subjects (following successful implantation) at 
approximately 140 sites. Each subject will be followed for 12 months, with follow-up visits at 6 and 12 
months. 
 
Objectives 
GUIDE-HF Randomized Arm: The objective of the GUIDE-HF Randomized Arm is to determine if PA 
pressure-guided HF management using CardioMEMS™ improves health outcomes in NYHA Class II, III, 
or IV HF patients with either elevated NT-proBNP (or BNP) and/or a prior HFH. 
 
GUIDE-HF Single Arm: The objective of the GUIDE-HF Single Arm is to demonstrate the equivalence of 
the effect of PA pressure-guided HF management on health outcomes between NYHA Class III HF 
patients with elevated NT-proBNP (or BNP) only and those with a prior HFH only. 
 
Endpoints 
Refer to Appendix C for event definitions used for the trial endpoints. 
4.3.1 
GUIDE-HF Randomized Arm 
The GUIDE-HF Randomized Arm will evaluate one primary endpoint, several secondary endpoints, and 
several descriptive endpoints. All endpoints will be compared between the Treatment and Control Groups 
unless otherwise noted.  
4.3.1.1 
Primary Endpoint 
The primary endpoint is a composite of recurrent HFHs or emergency department/hospital outpatient 
observation visits for intravenous diuretic therapy or all-cause mortality at 12 months post-implantation 
(referred to as the Composite Endpoint). Emergency department visits and hospital outpatient 
observation visits involving intravenous diuretics, along with HFHs, are included in the primary endpoint, 
as the duration of hospitalization can vary, and decompensation events requiring intravenous diuretic 
therapy impact subject quality-of-life and mortality, regardless of form (inpatient or outpatient). The 
following events will be included in the composite: 1) hospitalization (≥ 24 hours) with the primary reason 
for admission being acute decompensated HF and intravenous administration of diuretic therapy; 2) an 
unscheduled or unplanned admission to the emergency department, hospital outpatient observation visit, 
or hospital inpatient visit and intravenous administration of diuretic therapy; 3) all-cause mortality. All 
events contributing to the primary endpoint will be adjudicated by an independent Clinical Events 
Committee (CEC) (see section 5.10.4 for details). In rare instances, CEC discretion may be used to 
determine whether additional criteria would identify a decompensation event that could represent a valid 
contribution to the primary endpoint (e.g., ultra-filtration in lieu of diuretics). 
4.3.1.2 
Secondary Endpoints 
The secondary effectiveness endpoints are: 
• 
Composite of recurrent HFHs or emergency department/hospital outpatient observation visits for 
intravenous diuretic therapy 
• 
Health status at baseline, 6, and 12 months post-implantation as assessed by the EuroQol 5-
Dimension, 5-Level (EQ-5D-5L) Questionnaire 

 
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Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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• 
Health status at baseline, 6, and 12 months post-implantation as assessed by the Kansas City 
Cardiomyopathy Questionnaire (KCCQ-12) 
• 
Six Minute Hall Walk (6MHW) test at baseline, 6, and 12 months post-implantation 
• 
In addition, the individual components of the primary endpoint will each be evaluated as 
descriptive secondary effectiveness endpoints: 
o 
HFHs at 12 months post-implantation 
o 
Emergency department/hospital outpatient observation visits for intravenous diuretic 
therapy at 12 months post-implantation 
o 
All-cause mortality at 12 months post-implantation 
 
The secondary safety endpoint is freedom from device/system related complications (DSRCs) at 12 
months post-implantation. The secondary safety endpoint will be evaluated for all subjects enrolled in the 
Randomized Arm (i.e. with an attempted implant, whether successful or unsuccessful) and reported for 
the entire subject cohort and by subject group. 
4.3.1.3 
Descriptive Endpoints 
Descriptive endpoints are reported using only summary statistics and no hypothesis tests will be 
performed. All mortality- and hospitalization-related components of the primary endpoints will be 
adjudicated by the CEC. The following additional data will be collected and reported: 
• 
Cardiovascular mortality at 12 months post-implantation 
• 
All-cause hospitalizations at 12 months post-implantation 
• 
Frequency of subject PA pressure uploads through 12 months 
• 
HF medication changes through 12 months 
• 
PA pressure measurements from baseline through 12 months 
• 
NT-proBNP (or BNP) at baseline, 6, and 12 months 
• 
HFHs at 12 months post-implantation compared to HFHs in the 12 months prior to implantation 
4.3.2 
GUIDE-HF Single Arm 
The GUIDE-HF Single Arm will evaluate one primary endpoint, several secondary endpoints, and several 
descriptive endpoints. 
4.3.2.1 
Primary Endpoint 
The primary endpoint is a composite of recurrent HFHs or emergency department/hospital outpatient 
observation visits for intravenous diuretic therapy or all-cause mortality at 12 months post-implantation 
(same as for the Randomized Arm), to be compared between subjects with an elevated NT-proBNP (or 
BNP) only and subjects with a prior HFH only. Subjects who have both elevated NT-proBNP (or BNP) 
and a prior HFH will not be included in the analysis for the primary endpoint. All events contributing to the 
primary endpoint will be adjudicated by the CEC (see section 5.10.4 for details). In rare instances, CEC 
discretion may be used to determine whether additional criteria would identify a decompensation event 
that could represent a valid contribution to the primary endpoint (e.g., ultra-filtration in lieu of diuretics). 
4.3.2.2 
Secondary Endpoints 
The secondary effectiveness endpoints are: 
• 
Composite of recurrent HFHs or emergency department/hospital outpatient observation visits for 
intravenous diuretic therapy at 12 months post-implantation 
• 
HFHs at 12 months post-implantation compared to HFHs in the 12 months prior to implantation. 
All subjects who receive a CardioMEMS™ PA Sensor implant will be included in the analysis of 
this endpoint. 
• 
In addition, the individual components of the primary endpoint will each be evaluated as 
descriptive secondary effectiveness endpoints: 
o 
HFHs at 12 months post-implantation 

 
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Clinical Investigation Plan 
 
 
 
 
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o 
Emergency department/hospital outpatient observation visits for intravenous diuretic 
therapy at 12 months post-implantation 
o 
All-cause mortality at 12 months post-implantation 
 
The secondary safety endpoint is freedom from DSRCs at 12 months post-implantation. The secondary 
safety endpoint will be evaluated for all subjects enrolled in the Single Arm (i.e. with an attempted implant, 
whether successful or unsuccessful) and reported for the entire subject cohort and by subject group. 
4.3.2.3 
Descriptive Endpoints 
Descriptive endpoints are reported using only summary statistics and no hypothesis tests will be 
performed. All mortality- and hospitalization-related components of the primary endpoints will be 
adjudicated by the CEC. The following additional data will be collected and analyzed. The EQ-5D-5L, 
KCCQ-12, and 6MHW test will be collected and reported only for the first 1000 subjects enrolled and 
successfully implanted in the Single Arm. 
• 
Health status at baseline, 6, and 12 months post-implantation as assessed by EQ-5D-5L 
• 
Health status at baseline, 6, and 12 months post-implantation as assessed by the KCCQ-12 
• 
6MHW test at baseline, 6, and 12 months post-implantation 
• 
Cardiovascular mortality at 12 months post-implantation 
• 
All-cause hospitalizations at 12 months post-implantation 
• 
Frequency of subject PA pressure uploads through 12 months 
• 
HF medication changes through 12 months 
• 
PA pressure measurements from baseline through 12 months 
• 
NT-proBNP (or BNP) at baseline, 6 months, and 12 months 
 
Clinical Trial Population 
The intended population for this clinical trial includes patients over the age of 18 years with symptomatic 
NYHA class II, III, or IV HF and either a prior HFH within the past 12 months and/or elevated NT-proBNP 
(or BNP) within 30 days prior to consent, that meet the trial entry criteria defined below. Refer to Appendix 
C for NYHA class definitions. 
4.4.1 
Inclusion Criteria 
To participate in this clinical trial and receive a CardioMEMS™ HF System implant, subjects must meet 
all of the following inclusion criteria: 
1. Diagnosis and treatment for HF (regardless of LVEF) for > 90 days prior to the date of consent: 
a. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as 
recommended according to current AHA/American College of Cardiology (ACC) 
guidelines as standard-of-care for HF therapy in the United States, with any intolerance 
documented. 
2. GUIDE-HF Randomized Arm Only: NYHA Class II, III or IV HF symptoms documented within 30 
days prior to consent.  
3. GUIDE-HF Single Arm Only: NYHA Class III HF symptoms documented within 30 days prior to 
consent.  
4. HFH within 12 months prior to consent and/or elevated NT-proBNP (or BNP) within 30 days prior 
to consent defined as:  
a. Subjects with LVEF ≤ 40%: NT-proBNP ≥ 1000 pg/mL (or BNP ≥ 250 pg/mL). 
b. Subjects with LVEF > 40%: NT-proBNP ≥ 700 pg/mL (or BNP ≥ 175 pg/mL). 
c. Thresholds for NT-proBNP and BNP (for both LVEF ≤ 40% and LVEF > 40%) will be 
corrected for BMI using a 4% reduction per BMI unit over 25 kg/m2  
5. ≥ 18 years of age 
6. Chest circumference of < 65 inches, if BMI is > 35 kg/m2 
7. Written informed consent obtained from subject  

 
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Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
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8. Willing and able to upload PA pressure information and comply with the follow-up requirements 
4.4.2 
Exclusion Criteria 
Subjects who meet any of the following criteria must be excluded from the clinical trial: 
1. Intolerance to all neuro-hormonal antagonists (i.e., intolerance to angiotensin converting enzyme-
inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin-neprilysin inhibitors (ARNi), 
hydralazine/isosorbide dinitrate and beta-blockers) 
2. ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic 
circulatory support with inotropes) 
3. Received or are likely to receive an advanced therapy (e.g., mechanical circulatory support or 
cardiac transplant) in the next 12 months  
4. NYHA Class IV HF patients with: 
a. Continuous or chronic use of scheduled intermittent inotropic therapy for HF and an 
INTERMACS level of ≤ 4, OR 
b. Persistence of fluid overload with maximum (or dose equivalent) diuretic intervention 
5. Glomerular Filtration Rate (eGFR) < 25 mL/min/1.73m2 and non-responsive to diuretic therapy, or 
receiving chronic dialysis 
6. Inability to tolerate or receive dual antiplatelet therapy or anticoagulation therapy for one month 
post-implantation 
7. Significant congenital heart disease that has not been repaired and would prevent implantation of 
the CardioMEMS™ PA Sensor 
8. Implanted with mechanical right heart valve(s) 
9. Unrepaired severe valvular disease  
10. Pregnant or planning to become pregnant in the next 12 months 
11. An active, ongoing infection, defined as being febrile, an elevated white blood cell count, on 
intravenous antibiotics, and/or positive cultures (blood, sputum or urine). 
12. History of current or recurrent (≥ 2 episodes within 5 years prior to consent) pulmonary emboli 
and/or deep vein thromboses 
13. Major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary 
intervention, open heart surgery, or stroke, etc.) within 90 days prior to consent 
14. Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-
Defibrillator (CRT-D) for less than 90 days prior to consent 
15. Enrollment into another trial with an active treatment arm 
16. Anticipated life expectancy of < 12 months 
17. Any condition that, in the opinion of the Investigator, would not allow for utilization of the 
CardioMEMS™ HF System to manage the subject using information gained from hemodynamic 
measurements to adjust medications, including the presence of unexpectedly severe pulmonary 
hypertension (e.g., trans-pulmonary gradient >15) at implant RHC, a history of non-compliance, 
or any condition that would preclude CardioMEMS™ PA Sensor implantation 
4.4.3 
Enrollment of Medicare Beneficiaries 
This clinical trial will enroll appropriate Medicare beneficiaries that qualify based on the inclusion and 
exclusion criteria set forth in the trial. This IDE clinical trial adheres to all standards of Medicare coverage 
requirements set forth by the IDE and clinical trial coverage policies of the Center for Medicare and 
Medicare Services (CMS). Section 7, Risks and Benefits, describes how all enrolled subjects, including 
Medicare beneficiaries, may be affected by the CardioMEMS™ HF System under investigation. 
 
Subjects enrolled in the clinical trial are expected to be consistent with the Medicare population based on 
demographic characteristics and cardiovascular risk factors; therefore, the clinical trial results are 
expected to be generalizable to the Medicare population. 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 18 of 71 
 
 
 
 
Subject Recruitment 
For the recruitment of subjects, sites will screen charts from their own HF patient population and/or reach 
out to clinicians within their referral base. Any subject-facing recruitment materials or advertisements will 
require both Sponsor and IRB approval prior to use.  
 
Point of Enrollment 
In both the Randomized Arm and Single Arm, subjects will be considered enrolled once all entry criteria 
are met, informed consent is provided, and implantation of the CardioMEMS™ PA Sensor is attempted. 
Safety information and adverse events (AEs) will be reported (per section 8.2) for all enrolled subjects. 
However, subjects will only contribute towards the sample size and all other endpoint analyses following 
successful implantation and randomization (Randomized Arm) or following successful implantation 
(Single Arm). See Appendix L for a flow chart reflecting trial enrollment procedures. Subjects who provide 
written informed consent, but fail to meet entry criteria (or choose to no longer participate) prior to an 
attempted implantation will be considered screening failures. Subjects with an attempted, but 
unsuccessful, implant will be followed for 30 days post-implantation attempt for safety and/or will undergo 
a re-attempted implantation procedure (see section 5.4.4.1 for details).  
 
The Principal Investigator or delegated trial personnel will record enrollment information (including, but 
not limited to the date of implant (Single Arm), date of consent, and inclusion/exclusion information) in the 
subject records and complete and submit the applicable CRFs. Notification of enrollment to the Sponsor 
is considered to have occurred when the Sponsor has received documentation of the enrollment 
information via the applicable CRFs. 
 
Scheduled Procedures 
The Principal Investigator is responsible for ensuring all clinical trial data are collected as required per this 
CIP. 
 
Trained Sponsor personnel may provide technical expertise and technical guidance on the use of the 
CardioMEMS™ HF System, including the Merlin.net™ website, implant training and proctoring for 
implantations for sites using the CardioMEMS™ HF System for the first time. 
5.4.1 
Screening Procedures  
The following information will be evaluated from medical records and documented, to ensure each subject 
meets entry criteria prior to consent. Subjects are required to have either a HFH within the previous 12 
months or a documented elevated NT-proBNP (or BNP) within the previous 30 days (outside of clinical 
trial procedures per standard-of-care). Documentation of a prior HFH and/or elevated NT-proBNP (or 
BNP) is required for verification of inclusion and exclusion criteria. If necessary, screening procedures to 
address other entry criteria (such as EF and eGFR, if not previously documented) can be evaluated 
during the baseline visit following consent.  
• 
Duration of HF from first diagnosis 
• 
NYHA class evaluation within the previous 30 days 
• 
All HFHs within the previous one year, as provided by the subject’s cardiologist, internist, or 
referring physicians including gathering of source documentation of hospitalizations 
• 
Laboratory analyses for qualifying NT-proBNP (or BNP) within the previous 30 days for inclusion 
verification (outside of clinical trial procedures) 
• 
EF within six months prior to the consent date (can be from echo, nuclear testing, angiography, 
CT, MRI). If no documentation exists in the required timeframe, a limited echo to document EF 
only will be required during the baseline visit. 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 19 of 71 
 
 
• 
Calculation of BMI using subject height and weight (see Appendix H) and calculation of chest 
circumference measurement if BMI > 35kg/m2 
• 
Age 
• 
Cardiovascular history including: 
o 
previous cardiac procedures and CRT device information 
o 
relevant co-morbidities 
• 
HF medication review with documentation  
5.4.2 
Informed Consent 
As this IDE trial has two distinctly unique arms (Randomized Arm and Single Arm), one of two Informed 
Consent Forms will be utilized detailing requirements and considerations in each arm. The Principal 
Investigator or his/her authorized designee will conduct the informed consent process, as required by 
applicable regulations and the center’s IRB/EC. This process will include a verbal discussion with the 
subject on all aspects of the clinical trial that are relevant to the subject’s decision to participate such as 
details of the procedures, anticipated benefits, and potential risks of clinical trial participation. During the 
discussion, the Principal Investigator or his/her authorized designee will avoid any improper influence on 
the subject and will respect the subject’s legal rights. The subject shall be provided with the Informed 
Consent Form (for the applicable trial arm) written in a language that is understandable to the subject and 
has been approved by the center’s IRB/EC. The subject shall have adequate time to review, ask 
questions and consider participation. 
 
If the subject agrees to participate, the Informed Consent Form for the applicable trial arm must be signed 
and dated by the subject and by the person obtaining the consent. The signed original will be filed in the 
subject’s hospital or research charts, and a copy will be provided to the subject. 
 
The Principal Investigator or his/her authorized designee will document the informed consent process in 
the subject’s hospital and/or research charts. The date of signature will be entered on the applicable CRF. 
 
Failure to obtain informed consent from a subject prior to clinical trial enrollment should be reported to 
Sponsor within five working days and to the reviewing center’s IRB/EC according to the IRB’s/ EC’s 
reporting requirements. 
 
If, during the clinical trial, new information becomes available that can significantly affect a subject's 
health and medical care, the Principal Investigator or his/her authorized designee will provide this 
information to the subject. If relevant, the subject will be asked to confirm their continuing informed 
consent in writing. 
5.4.3 
Baseline Procedures 
The following assessments and information will be collected during the baseline visit prior to implant (see 
Table 2 for additional details). The Quality of Life assessments (KCCQ-12 and EQ-5D-5L) should be 
administered prior to all other baseline procedures. 
• 
KCCQ-12 Quality of Life assessment (see Appendix I for details) 
• 
EQ-5D-5L Quality of Life assessment (see Appendix I for details) 
• 
Verification of inclusion and exclusion criteria (as necessary from the screening procedures) 
• 
Documentation of key demographic information such as ethnicity, gender and age 
• 
Cardiovascular history including: 
o 
previous cardiac procedures and CRT device information 
o 
relevant co-morbidities 
• 
HF assessment including NYHA class evaluation 
• 
HF medication review with documentation  
• 
Laboratory analyses for baseline NT-proBNP (or BNP) 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 26 of 71 
 
 
• 
Medication review and documentation 
 Clinical Trial Committees 
5.10.1 Steering Committee 
A Steering Committee has been formed to advise the Sponsor on key aspects related to the 
development, execution, analysis and reporting, and overall conduct of the clinical trial. The primary 
function, responsibilities and membership of the Steering Committee will be described in detail in a 
Steering Committee charter. 
5.10.2 Publication Committee 
A Publication Committee shall be established to oversee trial publications, including publication planning 
and authorship determinations. Publication Committee membership may include members of the Steering 
Committee, Principal Investigators, a representative of the Sponsor and a statistician. The primary 
function, responsibilities and membership of the Publication Committee, as well as rules to define 
authorship, will be described in detail in a Publication Committee charter. 
5.10.3 Data Safety Monitoring Board (DSMB) 
An independent DSMB will review on a regular basis accumulating data from the clinical trial and will 
advise the Sponsor regarding the continuing safety of subjects and those yet to be recruited, as well as 
the continuing validity and scientific merit of the clinical trial. However, analysis of efficacy will not be used 
by the DSMB to consider continuance of the trial. DSMB members will not be Investigators in the clinical 
trial. At any time during the investigation, the DSMB may offer opinions or provide formal 
recommendations concerning aspects of the trial that impact subject safety (e.g. safety-related protocol 
changes or input regarding CardioMEMS™ HF System-related AE rates). The function, responsibilities 
and membership of the DSMB will be described in detail in a DSMB charter. 
5.10.4 CEC 
A CEC will be responsible for providing an independent review and adjudication of the following data: 
• 
Events that could contribute to primary endpoints for either trial arm, to determine which events 
meet primary endpoint qualification, including: 
o 
All cardiovascular hospitalizations, cardiovascular emergency department visits, and 
cardiovascular hospital outpatient visits, all defined as a hospital visit with the primary 
cause being cardiovascular in nature, as reported by the Investigator 
o 
All deaths 
o 
Any hospitalizations which, when reviewed by the Sponsor, could potentially meet 
endpoint qualification 
• 
HFHs that occurred within 12 months prior to baseline 
• 
All events that could contribute to the secondary safety endpoint for either trial arm including 
ADEs, SADEs, and UADEs 
 
All attempts will be made to blind the CEC to the treatment group assignment. The function, 
responsibilities and membership of the CEC will be described in greater detail in a CEC charter.  
6 
Statistical Considerations 
The following section describes the statistical methods for the clinical trial and justification of the design. 
Additional details on statistical analyses, including sensitivity analyses, poolability analyses, subgroup 
analyses and analysis of descriptive endpoint(s) will be described in a separate Statistical Analysis Plan 
(SAP). Hypothesis tests will be 1-sided and conducted at a significance level of 2.5% unless stated 
otherwise. 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 34 of 71 
 
 
• 
Bleeding 
o 
Epistaxis 
o 
Hemoptysis 
o 
GI bleed 
o 
Bleeding 
o 
Blood in stool 
o 
Catheter site bleeding 
o 
Catheter site ecchymosis 
o 
Hematuria 
o 
Nose bleeds  
• 
Hematoma 
o 
Hematoma 
o 
Catheter site hematoma 
o 
Vessel puncture site hematoma 
• 
Thrombus 
o 
Arterial thrombosis (limbs) 
o 
Blood clot 
• 
Myocardial infarction 
• 
Transient ischemic attack 
• 
Stroke 
• 
Death 
• 
Sensor embolization  
• 
Pulmonary artery perforation 
 
Refer to the CardioMEMS™ PA Sensor and Delivery Catheter, Model CM2000 User Manual for more 
information. If there are any questions regarding whether an event meets the associated definition (see 
Appendix C), the in-house Sponsor contact should be consulted.  
7.1.2 
Anticipated ADEs/SADEs 
The following is a list of possible anticipated ADEs/SADEs: 
• 
Hemoptysis  
• 
Sensor not deploying 
• 
Transient ischemic attack 
• 
Atypical chest pain 
• 
Sepsis leading to death 
• 
Atrial arrhythmia leading to death 
• 
Arterial embolism (upper extremity) 
• 
PA (in-situ) thrombus 
• 
Catheter site bleeding 
• 
Catheter site ecchymosis 
• 
Catheter site hematoma 
• 
Vessel puncture site pain 
• 
Cardiac monitoring abnormal 
• 
Heart rate irregular 
• 
Serum creatinine increased 
• 
Dyspnea 
• 
Congestive HF 
• 
Ventricular tachycardia 
• 
Dizziness 
• 
Vessel perforation  
• 
Sensor failure/malfunction 
• 
Sensor migration 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 35 of 71 
 
 
• 
System not transmitting 
7.1.3 
Non-AE Device Issue 
To adequately capture non-AE device issues, any device issues that fall outside of the AE definition (see 
Appendix C), a separate form will be used to capture such instances when the device fails to perform or 
does not function properly without an associated an adverse clinical outcome. 
 
Risk Control Measures 
Every possible effort will be taken to minimize the risks, including: 
• 
Careful selection of experienced Investigators for the clinical trial  
• 
Early (within 60 days of the first enrollment) and adequate monitoring for each clinical trial site per 
the trial monitoring plan 
• 
Conducting the clinical trial in accordance with the CIP, all applicable laws and regulations and 
any conditions of approval imposed by the appropriate IRB/EC or applicable regulatory 
authorities where the clinical trial is performed 
• 
Preparation of the CardioMEMS™ PA Sensor and performance of the implantation procedure in 
accordance with the IFUs 
• 
Training of Investigators both on the CIP and the CardioMEMS™ PA Sensor implantation 
procedure 
• 
Securing compliance of non-compliant sites (see section 11.3) 
• 
Assessment of continuing safety of subjects in the clinical trial by a DSMB 
 
Possible interactions with concomitant treatments 
The CardioMEMS™ PA Sensor is implanted in the PA via entry through the right side of the heart. If other 
device right heart leads are previously implanted, it is possible to cause dislodgement. Care should be 
taken to perform the implant procedure under fluoroscopy.  
 
Anticipated Benefits 
The benefit of hemodynamic-guided HF management in this population is unknown and information will 
be learned from this trial. Subjects with NYHA Class III HF and a prior HFH studied in the Treatment 
Group of the CHAMPION™ trial experienced a reduction in HF admissions. However, there is no 
guarantee that a similar benefit will occur in this slightly different population of NYHA Class II, III, or IV HF 
patients with a prior HFH and/or elevated NT-proBNP (or BNP). The information gathered will provide 
additional evidence regarding hemodynamic-guided HF management in at-risk NYHA Class II, III, or IV 
HF patients.  
 
Risk-to-Benefit Rationale 
Congestive HF is a progressive disease and HF patients are generally symptomatic. Symptoms of 
dyspnea and fatigue increase with elevations of pressures within the heart and lungs, leading to instances 
of acute HF decompensation. The CardioMEMS™ HF System enables clinicians to medically manage HF 
patients by adjusting treatments to keep PA pressures within target ranges to prevent or reduce instances 
of acute HF decompensation. In doing so, the CHAMPION™ trial demonstrated a reduction in rates of HF 
decompensation resulting in an HFH in NYHA Class III patients who had a HFH within the prior 12 
months. Treating with the knowledge of PA pressures may extend benefit to this at-risk population of HF 
patients with the goal of reducing decompensation events that result in HFHs or emergency 
department/hospital outpatient visits requiring intravenous diuretic therapy. The trial is designed to 
demonstrate this benefit to an expanded patient population. 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 36 of 71 
 
 
 
History of Device Modifications or Recall 
There have been no modifications or recall in relation to safety and clinical performance of the 
CardioMEMS™ HF System under investigation. 
8 
Requirements for Investigator Records and Reports 
 
Deviations from CIP 
A deviation is defined as an instance of failure to follow, intentionally or unintentionally, the requirements of 
the CIP. The Investigator should make every effort not to deviate from the CIP, and all deviations must be 
reported.  
 
If a subject is successfully implanted and/or randomized, but later found to not meet all inclusion/exclusion 
criteria, the subject will remain enrolled and a protocol deviation must be submitted.  
 
Additionally, in the event that the IFU is not followed and an alternative implantation approach is pursued, 
the alternative implantation approach and associated justification must be reported as a protocol 
deviation. The Sponsor will review and track deviation frequency and trends. All effort should be made to 
avoid deviations, and repeat offense will result in Sponsor intervention (see section 11.3). Deviations are 
expected to be infrequent. 
 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety and 
well-being of subjects; such non-compliance exposes subjects to unreasonable risks. Examples include 
failure to comply with prescribed clinical trial procedures with respect to: obtaining ICF properly, 
performing assessments within the applicable time period, following the CardioMEMS™ PA Sensor 
implantation procedure, following treatment guidelines (without documentation of the reason), following 
subject contact procedures (for the Randomized Arm), adhering to the inclusion/exclusion criteria, and 
reporting device-related AEs. Investigators should seek to minimize such risks by adhering to the CIP. 
 
The PI must maintain accurate, complete, and current records, including documents showing the date of 
and reason for each deviation from the CIP. Relevant information for each deviation will be documented 
as soon as possible on the applicable CRF, and submitted by the site to the Sponsor. 
 
The PI is required to adhere to local regulatory requirements for reporting deviations to IRB/EC. 
 
An Investigator shall notify the Sponsor and the reviewing IRB/EC of any deviation from the 
investigational plan to protect the life or physical well-being of a subject in an emergency. Such notice 
shall be given as soon as possible, but no later than five working days after the emergency occurred. 
Except in such an emergency, prior approval by the Sponsor is required for changes in or deviations from 
the CIP, and if these changes or deviations may affect the scientific soundness of the CIP or the rights, 
safety, or welfare of human subjects, FDA and IRB/EC is also required. 
 
Safety Reporting 
Safety surveillance and the safety reporting by the Investigator starts as soon as the subject is enrolled 
(all entry criteria are met, informed consent is provided, and implantation of the CardioMEMS™ PA 
Sensor is attempted) in either the Randomized Arm or the Single Arm.  
 
Safety surveillance and safety reporting will continue until the last investigational visit has been 
performed, the subject is deceased, the subject’s participation in the clinical trial is concluded by the 
Investigator, or the subject withdraws from the clinical trial. 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 37 of 71 
 
 
All reportable (per section 8.2.1) AE data including deaths will be collected throughout the clinical trial and 
will be reported to the Sponsor on the applicable CRFs. 
 
Reportable AEs will be monitored until they are adequately resolved or the subject has ended his/her 
participation in the trial, whichever comes first. The status of the subject’s condition will be documented at 
each visit. 
 
See Appendix C for event definitions regarding safety reporting. 
 
SAE Reporting 
 
The investigator should report all SAEs to the Sponsor as soon as possible but no later than outlined 
below.  
 
Clinical Site 
Reporting timelines 
All Sites 
SAEs must be reported to the Sponsor no later than 3 calendar days from the 
day the site personnel became aware of the event or as per the investigative 
site’s local requirements, if the requirement is more stringent than those outlined. 
 
The date the site staff became aware the event met the criteria of an SAE must be recorded in the source 
document.  The Investigator will further report the SAE to the local IRB/EC according to the institution’s 
IRB/EC reporting requirements. 
8.2.1 
Criteria and Guidelines for Reportable Events 
For the purposes of this clinical trial, the following events will be reported to the Sponsor for the duration 
of the trial: 
• 
All hospital admissions, including: 
o 
All SAEs occurring during a hospital admission outside of the original indication for 
admission (e.g. stroke, myocardial infarction, etc.) 
• 
Emergency department/hospital outpatient observation visits that are cardiovascular in nature 
• 
All deaths 
• 
HFHs that occurred within 12 months prior to baseline 
• 
SAEs, ADEs, SADEs, and UADEs 
 
Of the reportable events, the following events will be adjudicated by an independent CEC: 
• 
Events that could contribute to primary endpoints for either trial arm, to determine which events 
meet primary endpoint qualification, including: 
o 
All cardiovascular hospitalizations, cardiovascular emergency department visits, and 
cardiovascular hospital outpatient visits, all defined as a hospital visit with the primary 
cause being cardiovascular in nature, as reported by the Investigator 
o 
All deaths  
o 
Any other hospitalizations which, when reviewed by the Sponsor, could potentially meet 
endpoint qualification 
• 
HFHs that occurred within 12 months prior to baseline 
• 
All events that could contribute to the secondary safety endpoint for either trial arm including 
ADEs, SADEs, and UADEs 
 
A list of anticipated AEs is included in sections 7.1.1 and 7.1.2. The Sponsor will ensure that all applicable 
events are reported to the relevant authorities as per regulations. The sites should notify the Sponsor of 
reportable AEs by creating and saving the applicable CRFs within the electronic data capture (EDC) 
system. The description of the AE, date of the AE, treatment and resolution of the AEs will be reported, as 
applicable, to the relevant authorities per regulations. Additional information may be requested, when 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 38 of 71 
 
 
required, by the Sponsor in order to support the reporting or adjudication of AEs. The Investigator must 
notify the IRB/EC, if appropriate, in accordance with national and local laws and regulations, of the AEs 
reported to the Sponsor.  
8.2.2 
Criteria and Guidelines for Non-Reportable Events 
The following events are not reportable to the Sponsor: 
• 
Non-serious AEs unrelated to the investigational device/procedure, including those occurring 
during the course of a hospitalization that are not the primary reason for the hospitalization 
• 
Non-cardiovascular or trauma events unrelated to HF, not resulting in a hospital admission 
• 
Minor outpatient non-cardiovascular procedures, such as colonoscopy or cataract surgery 
8.2.3 
Subject Death 
Subject deaths will be documented and reported to the Sponsor as soon as possible after the site 
becomes aware of the event via the applicable CRF. If a subject death is not reported within the required 
time, it will be considered a protocol deviation. 
 
The CEC will review and classify all subject deaths. Notification of death must include a detailed 
statement of the pertinent event and be submitted on the applicable CRF. It is the Investigator’s 
responsibility to notify the IRB/EC per the IRB/EC policy. Details of death and the following information, if 
available, should be provided to the Sponsor: 
• 
Date of death 
• 
Primary/organ cause of death 
• 
Any circumstances surrounding the death 
• 
Approximate time interval to death from the initiating event. 
• 
Autopsy report (if performed) 
• 
Whether it was trial device- and/or procedure-related 
8.2.4 
UADEs 
The Sponsor requires the Investigator to report any UADE to the Sponsor within 3 calendar days of the 
investigator’s knowledge of the event, unless local requirements are more stringent, and to the IRB/EC 
per IRB/EC requirements. The same reporting requirement applies to the investigational sites located in 
Canada.  
 
In the case of a UADE reported to the Sponsor, the Sponsor will take any steps necessary to investigate 
the event, and, as appropriate, will be responsible for notifying the FDA, Health Canada, and all 
participating IRBs/ECs and Investigators within 10 working days. 
 
Should the Sponsor determine, either through physician reports or in-house testing, that a UADE 
presents an unreasonable risk to participating patients, Sponsor will suspend the clinical investigation and 
notify the FDA, Health Canada, and all participating IRBs/ECs and Investigators. 
 
Source records 
Source documents will be created and maintained by the investigational site team throughout the clinical 
trial. The data reported on the CRFs will be derived from, and be consistent with, these source 
documents, and any discrepancies will be explained in writing. 
 
Relevant source documents for all reportable events which will be adjudicated by the CEC (see section 
8.2.1) must be provided. Sites are responsible to acquire, de-identify and label records with subject ID 
and submit them to the Sponsor in a timely manner.  

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 39 of 71 
 
 
 
Records Retention 
The Sponsor and the Principal Investigators will maintain the clinical trial documents as required. 
Measures will be taken to prevent accidental or premature destruction of these documents. The Principal 
Investigator or the Sponsor may transfer custody of records to another person/party and document the 
transfer at the investigational site or the Sponsor’s facility, as appropriate. 
 
These documents must be retained by the investigational site for a period of two years after the 
conclusion of the clinical trial and made available for monitoring or auditing by the Sponsor’s 
representative or representatives of the applicable regulatory agencies. 
 
All original source documents must be stored for the maximum time required by the regulations at the 
hospital, research institute, or practice in question. If original source documents can no longer be 
maintained at the site, the Investigator will notify the Sponsor.  
9 
Clinical Data Handling 
The Sponsor will be responsible for the handling of clinical data generated in this trial, submitted by the 
site or obtained from Merlin.net™. The Sponsor and/or its affiliates will be responsible for compiling and 
submitting all required reports to governmental agencies. Data will be analyzed by the Sponsor and may 
be transferred to the Sponsor’s locations worldwide and/or any other worldwide regulatory authority in 
support of a market-approval application. 
 
Protection of Personally Identifiable Information 
The Sponsor respects and protects personally identifiable information collected or maintained for this 
clinical trial. The privacy of each subject and confidentiality of his/her information will be preserved in 
reports and when publishing any data. Confidentiality of data will be observed by all parties involved at all 
times throughout the clinical trial. All data will be secured against unauthorized access. 
 
Data Management Plan (DMP) 
A DMP will describe procedures used for data review, database creation and cleaning, and issuing and 
resolving data queries. If appropriate, the DMP may be updated throughout the clinical trial duration. All 
revisions will be tracked and document controlled. 
 
Subject data will be captured in a validated EDC system hosted by the Sponsor and compliant with FDA 
regulations. 
 
Only authorized site personnel will be permitted to enter the CRF data through the EDC system deployed 
by the Sponsor. An electronic audit trail will be used to track any subsequent changes of the entered 
data. 
 
Document and Data Control 
9.3.1 
Traceability of Documents and Data 
The Investigator will ensure accuracy, completeness, legibility, and timeliness of the data reported to the 
Sponsor on the CRFs and in all required reports. 
9.3.2 
Recording Data 
The CRFs will be reviewed by the authorized site personnel. An appropriate comment will be provided to 
explain changes to data reported on the CRFs. 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 40 of 71 
 
 
10 Monitoring 
It is the responsibility of the Sponsor to ensure the clinical trial is conducted, recorded and reported 
according to the approved CIP, subsequent amendment(s), applicable regulations and guidance 
documents. 
 
Monitoring will be conducted according to the Sponsor’s Clinical Monitoring work instruction. Prior to 
beginning the clinical trial, the Sponsor will contact the Investigator or designee to discuss the clinical trial 
and data requirements. The Investigator shall make subject and clinical trial records available to the 
clinical monitor for monitoring. A designated monitor will periodically review the subject records and 
associated source documents. 
11 Compliance Statement 
 Statement of Compliance 
In addition to applicable regional or local laws and regulations, this clinical trial will be conducted in 
compliance with the most current version of the World Medical Association (WMA) Declaration of Helsinki 
and 21 CFR Parts 50, 54, 56 and 812. In the event of any conflicts, local laws and regulations will have 
precedence and in such cases, good faith efforts will be made to adhere to the intent of the other 
documents. 
 
The Investigator will sign a Clinical Trial Agreement and agrees to be compliant with it. The Investigator 
will not start enrolling subjects or requesting informed consent from any subject prior to obtaining IRB/EC 
approval and relevant Regulatory Authority approval, if applicable, and authorization from the Sponsor in 
writing for the clinical trial. If additional requirements are imposed by the IRB/EC or relevant Regulatory 
Authority, those requirements will be followed. If any action is taken by an IRB/EC or a relevant 
Regulatory Authority with respect to the clinical trial, that information will be forwarded to the Sponsor. 
 
The Sponsor has taken up general liability insurance in accordance with the requirements of the 
applicable local laws. An appropriate Sponsor’s country representative will be utilized to understand the 
requirements for the type of insurance that will be provided for subjects, and such information will be 
incorporated into the site informed consent process, as applicable. If required, additional subject 
coverage or a clinical trial specific insurance will be provided by the Sponsor. 
 Quality Assurance Audits and Regulatory Inspections 
The Investigator and/or delegate should contact the Sponsor immediately upon notification of a regulatory 
authority inspection at the site. A monitor or designee will assist the Investigator and/or delegate in 
preparing for the audit. The Sponsor may perform quality assurance audits, as required. 
 
The Principal Investigator or institution will provide direct access to source and CRF data during and after 
the clinical trial for monitoring, audits, IRB/EC review and regulatory authority inspections, as required. 
The Principal Investigator or institution will obtain permission for direct access to source documents from 
the subject, hospital administration and national regulatory authorities before starting the clinical trial. 
 Repeated and Serious Non-Compliance 
The Sponsor will review compliance with the CIP and trends and deviations on a regular basis. In the 
event of repeated non-compliance or a one-time serious non-compliance, as determined by the Sponsor, 
a monitor or designee will attempt to secure compliance by one or more of the following actions and will 
document all attempts or actions: 
• 
Retrain applicable site research staff 
• 
Create a compliance plan 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 44 of 71 
 
 
Appendix B: Acronyms 
 
6MHW 
Six Minute Hall Walk 
ACC 
American College of Cardiology 
ACE-I 
Angiotensin Converting Enzyme-Inhibitor 
ADE 
Adverse Device Effect 
ADHF 
Acutely Decompensated Heart Failure 
AE 
Adverse Event 
AHA 
American Heart Association 
ARB 
Angiotensin Receptor Blocker 
ARNi 
Angiotensin-Neprilysin Inhibitor 
BMI 
Body Mass Index 
BNP 
Brain Natriuretic Peptide 
CEC 
Clinical Events Committee 
CHAMPION 
CardioMEMS™ HF Sensor Allows Monitoring of Pressures to 
Improve Outcomes in NYHA Functional Class III HF Patients 
CI 
Confidence Interval 
CIP 
Clinical Investigation Plan 
CMS 
Center for Medicare and Medicaid Services 
CRF 
Case Report Form 
CRT 
Cardiac Resynchronization Therapy 
CRT-D 
Cardiac Resynchronization Therapy – Defibrillator 
CRT-P 
Cardiac Resynchronization Therapy – Pacemaker 
DMP 
Data Management Plan 
DSMB 
Data Safety Monitoring Board 
DSRC 
Device/System Related Complication 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
EF 
Ejection Fraction 
eGFR 
Glomerular Filtration Rate 
EQ-5D-5L 
EuroQol 5-Dimension, 5-Level 
FDA 
Food and Drug Administration 
GDMT 
Guideline Directed Medical Therapy 
GUIDE-HF 
Hemodynamic-GUIDEd Management of Heart Failure 
HF 
Heart Failure 
HFH 
Heart Failure Hospitalization 
HFpEF 
Heart Failure with Preserved Ejection Fraction 
HFrEF 
Heart Failure with Reduced Ejection Fraction 
HR 
Hazard Ratio 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
KCCQ-12 
Kansas City Cardiomyopathy Questionnaire 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 45 of 71 
 
 
LSM 
Least Squares Means 
LVAD 
Left Ventricular Assist Device 
LVEF 
Left Ventricular Ejection Fraction 
MAC 
Medicare Administrative Contractor 
MEMS 
Micro-ElectroMechanical Systems 
NT-proBNP 
N-Terminal pro-Brain Natriuretic Peptide 
NYHA 
New York Heart Association 
PA 
Pulmonary Artery 
PAS 
Post-Approval Study 
PCWP 
Pulmonary Catheter Wedge Pressure 
PMA 
Pre-Market Approval 
RHC 
Right Heart Catheterization 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
TOST 
Two, One-Sided Test 
UADE 
Unanticipated Adverse Device Effect 
VAS 
Visual Analogue Scale 
VRDC 
Virtual Research Data Center 
WMA 
World Medical Association 
 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 47 of 71 
 
 
Note:  A planned hospitalization for a pre-existing condition, or a procedure required by the 
CIP is not considered an SAE. 
• 
Adverse Device Effect (ADE): An AE related to the use of an investigational medical device. 
This definition includes AEs resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the investigational 
medical device. This definition includes any event resulting from the use error or from intentional 
misuse of the investigational medical device. 
• 
Serious Adverse Device Effect (SADE): ADE that has resulted in any of the consequences 
characteristic of a serious AE. 
• 
Unanticipated Adverse Device Effect (UADE): As defined in 21 CFR §812.3, any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the CIP or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects.  
• 
Non-AE Device Issue: any instance when the device fails to perform or does not function 
properly without an associated an adverse clinical outcome. 
• 
Device/System Related Complication (DSRC): An AE that is related or possibly related to the 
system (CardioMEMS™ PA Sensor or other components of the CardioMEMS™ HF System) and 
has at least one of the following characteristics: 
o 
is treated with invasive means (other than intramuscular medication or a right heart 
catheterization which is used for diagnostic purposes) 
o 
resulted in the death of the subject 
o 
resulted in the explant of the device 
 
 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 50 of 71 
 
 
Table D1: Estimated Composite Event Rates from Previous HF Studies 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 56 of 71 
 
 
Appendix I: Subject-Reported Outcome Measures 
 
The Trial Coordinator or designee will administer subject-reported outcome questionnaires. It is important 
the subject understands the meaning of all words and instructions in the questionnaires. The subject 
should be instructed to ask any questions about the questionnaires if further explanation is needed. It is 
recommended that the subject-reported outcome measures are issued prior to all other procedures during 
each visit. Once the questionnaires are completed, the Trial Coordinator or designee will review for 
completeness to verify that all questions have been answered according to the directions provided. 
 
The following subject-reported outcome measures will be collected according to the trial requirements: 
• 
EQ-5D-5L to be obtained at baseline, 6 months and 12 months 
• 
KCCQ-12 to be obtained at baseline, 6 months and 12 months 
 
EQ-5D-5L 
The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group in order to 
provide a simple, generic measure of health for clinical and economic appraisal. Applicable to a wide 
range of health conditions and treatments, it provides a simple descriptive profile and a single index value 
for health status that can be used in the clinical and economic evaluation of healthcare as well as in 
population health surveys. The questionnaire will take approximately two minutes to complete.  
 
The EQ-5D-5L consists of two components – the EQ-5D-5L descriptive system and the EQ Visual 
Analogue scale (VAS). For the descriptive system, five dimensions are measured (mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression). Each dimension has five levels: 1=none, 
2=slight, 3=moderate, 4=severe, and 5=extreme. The respondent indicates his or her health state by 
ticking in the box against the most appropriate statement in each of the five dimensions. The VAS is 
scored from 0 (worst health) to 100 (best health).  
 
KCCQ-12 
The KCCQ-12 is a standardized, validated (53), and disease-specific health status measure for HF 
patients. It is a self-administered questionnaire that quantifies physical limitations, symptoms, self-
efficacy, social interference and quality of life. It is shown to have high test-retest reliability and high 
responsiveness. It is prognostic of both clinical events and costs. The KCCQ-12 will be utilized as a 
performance measure of healthcare quality. It provides a reliable and effective tool to assess whether HF 
patients’ conditions have changed over time. The questionnaire has twelve questions and takes 
approximately three minutes to complete.  
 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 59 of 71 
 
 
Appendix L: Enrollment Flow Chart 
 
 
 
 

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 65 of 71 
 
 
Secondary 
Endpoints  
GUIDE-HF Randomized Arm: The secondary effectiveness endpoints, to be compared 
between the Treatment and Control Groups, are: 
• 
Composite of recurrent HFHs or emergency department/hospital outpatient 
observation visits for intravenous diuretic therapy 
• 
Health status at baseline, 6, and 12 months post-implantation as assessed by 
the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire 
• 
Health status at baseline, 6, and 12 months post-implantation as assessed by 
the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) 
• 
Six Minute Hall Walk (6MHW) test at baseline, 6, and 12 months post-
implantation 
• 
In addition, the individual components of the primary endpoint will each be 
evaluated as descriptive secondary effectiveness endpoints: 
o 
HFHs at 12 months post-implantation 
o 
Emergency department/hospital outpatient observation visits for 
intravenous diuretic therapy at 12 months post-implantation 
o 
All-cause mortality at 12 months post-implantation 
The secondary safety endpoint is freedom from device/system related complications 
(DSRCs) at 12 months post-implantation. The secondary safety endpoint will be 
evaluated for all subjects enrolled in the Randomized Arm (i.e. with an attempted 
implant, whether successful or unsuccessful) and reported for the entire subject cohort 
and by subject group. 
 
GUIDE-HF Single Arm: The secondary effectiveness endpoints are: 
• 
Composite of recurrent HFHs or emergency department/hospital outpatient 
observation visits for intravenous diuretic therapy at 12 months post-
implantation 
• 
HFHs at 12 months post-implantation compared to HFHs in the 12 months prior 
to implantation. All subjects who receive a CardioMEMS™ PA Sensor implant 
will be included in the analysis of this endpoint. 
• 
In addition, the individual components of the primary endpoint will each be 
evaluated as descriptive secondary effectiveness endpoints: 
o 
HFHs at 12 months post-implantation 
o 
Emergency department/hospital outpatient observation visits for 
intravenous diuretic therapy at 12 months post-implantation 
o 
All-cause mortality at 12 months post-implantation 
The secondary safety endpoint is freedom from DSRCs at 12 months post-implantation. 
The secondary safety endpoint will be evaluated for all subjects enrolled in the Single 
Arm (i.e. with an attempted implant, whether successful or unsuccessful) and reported 
for the entire subject cohort and by subject group. 
Inclusion Criteria 
1. Diagnosis and treatment for HF (regardless of LVEF) for > 90 days prior to the date 
of consent: 
a. Subjects should be on stable, optimally titrated medical therapy for at least 30 
days, as recommended according to current AHA/American College of 
Cardiology (ACC) guidelines as standard-of-care for HF therapy in the United 
States, with any intolerance documented. 
2. GUIDE-HF Randomized Arm Only: NYHA Class II, III or IV HF symptoms 
documented within 30 days prior to consent.  

 
Study Document No.: 
 
Study Name: GUIDE-HF IDE 
 
Clinical Investigation Plan 
 
 
 
 
Page 66 of 71 
 
 
3. GUIDE-HF Single Arm Only: NYHA Class III HF symptoms documented within 30 
days prior to consent.  
4. HFH within 12 months prior to consent and/or elevated NT-proBNP (or BNP) within 
30 days prior to consent defined as:  
a. Subjects with LVEF ≤ 40%: NT-proBNP ≥ 1000 pg/mL (or BNP ≥ 250 pg/mL). 
b. Subjects with LVEF > 40%: NT-proBNP ≥ 700 pg/mL (or BNP ≥ 175 pg/mL). 
c. Thresholds for NT-proBNP and BNP (for both LVEF ≤ 40% and LVEF > 40%) 
will be corrected for BMI using a 4% reduction per BMI unit over 25 kg/m2  
5. ≥ 18 years of age 
6. Chest circumference of < 65 inches, if BMI is > 35 kg/m2 
7. Written informed consent obtained from subject  
8. Willing and able to upload PA pressure information and comply with the follow-up 
requirements 
Exclusion Criteria 
1. Intolerance to all neuro-hormonal antagonists (i.e., intolerance to angiotensin 
converting enzyme-inhibitors (ACE-I), angiotensin receptor blockers (ARB), 
angiotensin-neprilysin inhibitors (ARNi), hydralazine/isosorbide dinitrate, and beta-
blockers) 
2. ACC/AHA Stage D refractory HF (including having received or currently receiving 
pharmacologic circulatory support with inotropes) 
3. Received or are likely to receive an advanced therapy (e.g., mechanical circulatory 
support or cardiac transplant) in the next 12 months  
4. NYHA Class IV HF patients with: 
a. Continuous or chronic use of scheduled intermittent inotropic therapy for HF 
and an INTERMACS level of ≤ 4, OR 
b. Persistence of fluid overload with maximum (or dose equivalent) diuretic 
intervention 
5. Glomerular Filtration Rate (eGFR) < 25 mL/min/1.73m2 and non-responsive to 
diuretic therapy, or receiving chronic dialysis 
6. Inability to tolerate or receive dual antiplatelet therapy or anticoagulation therapy 
for one month post-implantation 
7. Significant congenital heart disease that has not been repaired and would prevent 
implantation of the CardioMEMS™ PA Sensor 
8. Implanted with mechanical right heart valve(s) 
9. Unrepaired severe valvular disease  
10. Pregnant or planning to become pregnant in the next 12 months 
11. An active, ongoing infection, defined as being febrile, an elevated white blood cell 
count, on intravenous antibiotics, and/or positive cultures (blood, sputum or urine). 
12. History of current or recurrent (≥ 2 episodes within 5 years prior to consent) 
pulmonary emboli and/or deep vein thromboses 
13. Major cardiovascular event (e.g., unstable angina, myocardial infarction, 
percutaneous coronary intervention, open heart surgery, or stroke, etc.) within 90 
days prior to consent 
14. Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or 
CRT-Defibrillator (CRT-D) for less than 90 days prior to consent 
15. Enrollment into another trial with an active treatment arm 
16. Anticipated life expectancy of < 12 months 
17. Any condition that, in the opinion of the Investigator, would not allow for utilization 
of the CardioMEMS™ HF System to manage the subject using information gained 
from hemodynamic measurements to adjust medications, including the presence of 
unexpectedly severe pulmonary hypertension (e.g., trans-pulmonary gradient >15) 
at implant RHC, a history of non-compliance, or any condition that would preclude 
CardioMEMS™ PA Sensor implantation