Implanted Pulmonary Artery Pressure Sensor for Heart Failure Management

The Centers for Medicare & Medicaid Services (CMS) proposes to cover implantable pulmonary artery pressure sensor(s) (IPAPS) for heart failure (HF) management under Coverage with Evidence Development (CED) according to the provisions in sections (B) and (C) below.

We propose that implantation of an IPAPS is covered for HF management when furnished according to a Food and Drug Administration (FDA) market-authorized indication and all of the following conditions are met:

The patient meets all of the following criteria:

a)    Diagnosis of chronic HF of at least 3 months duration and in New York Heart Association (NYHA) functional Class II or III within the past 30 days, prior to PAPS implantation, regardless of left ventricular ejection fraction (LVEF).

b)   History of HF hospitalization or urgent HF visit (emergency room or other outpatient visit requiring intravenous diuretic therapy) within the past 12 months, or elevated natriuretic peptides within the past 30 days.

c)    On maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months prior to PAPS implantation.

d)   Evaluated for, and received if appropriate, an implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy (CRT)-Pacemaker (CRT-P), or CRT-Defibrillator (CRT-D). Implantation of the device must occur at least 3 months prior to PAPS implantation.

e)    No major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary intervention, open heart surgery, or stroke) within the last 3 months prior to PAPS implantation.

f)    Possessing adequate technology to ensure reliable remote connectivity to the IPAPS device.

g)   Must not have PAPS implantation occur during a hospital admission for an acute HF episode. 

The IPAPS items and services are furnished by practitioners who meet the following criteria, as applicable:

a)    Physicians referring Medicare patients and managing them post implantation must be cardiologists with experience in advanced HF management.

b)   Physicians implanting an IPAPS must have advanced training and experience in pulmonary arterial catheterization and intervention.

The IPAPS items and services are furnished in the context of a CMS-approved CED study. CMS-approved CED study protocols must: include only those patients who meet the criteria in section B.1; furnish items and services only through practitioners who meet the criteria in section B.2; and include all of the following:

a)    Primary outcomes of “HF hospitalization” (the cumulative number of HF hospital admissions, and HF emergency room or other outpatient visits requiring intravenous diuretics), all-cause mortality, or a composite of these, through a minimum of 24 months. Each component of a composite outcome must be individually reported.

b)   An active comparator.

c)    A care management plan that:

• Identifies members, roles and responsibilities of the physician-led HF clinical team (e.g., physicians, physician assistants, nurse practitioners, nurses) that performs the follow-up IPAPS patient monitoring and medication management; and
• Specifies the medication management protocols the patient and HF clinical team must follow.

d)   Design sufficient to demonstrate clinical utility of the IPAPS for HF management using direct measures of clinical behavior (e.g., counts of patient/physician interactions, counts and type of medication changes, counts of unscheduled outpatient clinic visits, counts of days within clinician set thresholds) to effectively manage and improve patient outcomes.

e)    Design sufficient for subgroup analyses by:

• CRT and/or ICD status (with/without);
• Age (75+ years);
• Sex;
• Race and ethnicity;
• LVEF (by guideline-defined subgroups);
• NYHA Class II vs III (as appropriate based on the FDA-approved label);
• Stage IV or greater chronic kidney disease;
• HF hospitalization in the past 12 months vs elevated natriuretic peptides alone in the last 30 days.

f)    In addition, CMS-approved CED studies must adhere to the scientific standards (criteria 1-17 below) that have been identified by the Agency for Healthcare Research and Quality (AHRQ) as set forth in Section VI. of CMS’ Coverage with Evidence Development Guidance Document, published August 7, 2024 (the “CED Guidance Document”).

1. Sponsor/Investigator:  The study is conducted by sponsors/investigators with the resources and skills to complete it successfully.
2. Milestones:  A written plan is in place that describes a detailed schedule for completion of key study milestones, including study initiation, enrollment progress, interim results reporting, and results reporting, to ensure timely completion of the CED process.
3. Study Protocol:  The CED study is registered with ClinicalTrials.gov and a complete final protocol, including the statistical analysis plan, is delivered to CMS prior to study initiation. The published protocol includes sufficient detail to allow a judgment of whether the study is fit-for-purpose and whether reasonable efforts will be taken to minimize the risk of bias.  Any changes to approved study protocols should be explained and publicly reported.
4. Study Context: The rationale for the study is supported by scientific evidence and study results are expected to fill the specified CMS-identified evidence deficiency and provide evidence sufficient to assess health outcomes.
5. Study Design:  The study design is selected to safely and efficiently generate valid evidence of health outcomes. The sponsors/investigators minimize the impact of confounding and biases on inferences through rigorous design and appropriate statistical techniques. If a contemporaneous comparison group is not included, this choice should be justified, and the sponsors/investigators discuss in detail how the design contributes useful information on issues such as durability or adverse event frequency that are not clearly answered in comparative studies.
6. Study Population: The study population reflects the demographic and clinical diversity among the Medicare beneficiaries who are the intended population of the intervention, particularly when there is good clinical or scientific reason to expect that the results observed in premarket studies might not be observed in older adults or subpopulations identified by other clinical or demographic factors. At a minimum, this includes attention to the intended population’s racial and ethnic backgrounds, gender, age, disabilities, important comorbidities, and, dependent on data availability, relevant health related social needs. For instance, more than half of Medicare beneficiaries are women so study designs should, as appropriate, consider the prevalence in women of the condition being studied as well as in the clinical trial and subsequent data reporting and analyses.
7. Subgroup Analyses: The study protocol explicitly discusses beneficiary subpopulations affected by the item or service under investigation, particularly traditionally unerrepresented groups in clinical studies, how the inclusion and exclusion requirements effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. In the protocol, the sponsors/investigators describe plans for analyzing demographic subpopulations as well as clinically-relevant subgroups as identified in existing evidence. Description of plans for exploratory analyses, as relevant subgroups emerge, are also included.
8. Care Setting: When feasible and appropriate for answering the CED question, data for the study should come from beneficiaries in their expected sites of care.
9. Health Outcomes: The primary health outcome(s) for the study are those important to patients and their caregivers and that are clinically meaningful. A validated surrogate outcome that reliably predicts these outcomes may be appropriate for some questions. Generally, when study sponsors propose using surrogate endpoints to measure outcomes, they should cite validation studies published in peer-reviewed journals to provide a rationale for assuming these endpoints predict the health outcomes of interest. The cited validation studies should be longitudinal and demonstrate a statistical association between the surrogate endpoint and the health outcomes it is thought to predict.
10. Objective Success Criteria:  In consultation with CMS and AHRQ, sponsors/investigators establish an evidentiary threshold for the primary health outcome(s) so as to demonstrate clinically meaningful differences with sufficient precision.
11. Data Quality:  The data are generated or selected with attention to provenance, bias, completeness, accuracy, sufficiency of duration of observation to demonstrate durability of health outcomes, and sufficiency of sample size as required by the question.
12. Construct Validity:  Sponsors/investigators provide information about the validity of drawing warranted conclusions about the study population, primary exposure(s) (intervention, control), health outcome measures, and core covariates when using either primary data collected for the study about individuals or proxies of the variables of interest, or existing (secondary) data about individuals or proxies of the variables of interest.
13. Sensitivity Analyses:  Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate.
14. Reporting: Final results are provided to CMS and submitted for publication or reported in a publicly accessible manner within 12 months of the study’s primary completion date. Wherever possible, the study is submitted for peer review with the goal of publication using a reporting guideline appropriate for the study design and structured to enable replication. If peer-reviewed publication is not possible, results may also be published in an online publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials.gov, or in journals willing to publish in abbreviated format (e.g., for studies with incomplete results).
15. Sharing:  The sponsors/investigators commit to making study data publicly available by sharing data, methods, analytic code, and analytical output with CMS or with a CMS-approved third party. The study should comply with all applicable laws regarding subject privacy, including 45 CFR § 164.514 within the regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient Records.
16. Governance: The protocol describes the information governance and data security provisions that have been established to satisfy Federal security regulations issued pursuant to HIPAA and codified at 45 CFR Parts 160 and 164 (Subparts A & C), United States Department of Health and Human Services (HHS) regulations at 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient and HHS regulations at 45 CFR Part 46, regarding informed consent for clinical study involving human subjects. In addition to the requirements under 42 CFR and 45 CFR, studies that are subject to FDA regulation must also comply with regulations at 21 CFR Parts 50 and 56 regarding the protection of human subjects and institutional review boards, respectively.
17. Legal:  The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals, although it is acceptable for a study to test a reduction in toxicity of a product relative to standard of care or an appropriate comparator.  For studies that involve researching the safety and effectiveness of new drugs and biological products aimed at treating life-threatening or severely-debilitating diseases, refer to additional requirements set forth in 21 CFR § 312.81(a).

Consistent with section 1142 of the Act, AHRQ supports clinical research studies that CMS determines meet all the criteria and standards identified above.

All other uses of IPAPS are non-covered.

See Appendix A for proposed Medicare National Coverage Determinations Manual language.

CMS is seeking comments on our proposed decision.  We will respond to public comments in a final decision memorandum, as required by § 1862(l)(3) of the Act.

Table of Contents

1.      Proposed Decision
1.       Proposed Decision
   
2.      Coverage Criteria
   
   1.      Patient Criteria
      
   2.      Physician Criteria
      
   3.      CED Study Criteria
3.      Other Uses of IPAPS


2.      Clinical Review
   
   1.      Background
      
      1.      Heart Failure Definitions & Classification
         
      2.      Heart Failure Disease Burden & Risk
         
      3.      Heart Failure Disease Management
         
      4.      Remote Monitoring for Heart Failure Management
         
      5.      Pulmonary Artery Pressure Monitoring
         
   2.      Food and Drug Administration Status
      
      1.      CardioMEMS (Abbott Medical)
         
      2.      Cordella (Edwards Lifesciences)
      
      
3.      Evidence
   
   1.      Evidence Questions
      
   2.      Technology Assessments
      
   3.      Medicare Evidence Development and Coverage Advisory Committee (MEDCAC)
      
   4.      Clinical Literature Search
      
      1.      Summary of Clinical Literature Search
         
      2.      CardioMEMS
         
      3.      Cordella
         
   5.      Assessment of the Evidence
   6.      Limitations of Evidence
   7.      Evidence-Based Guidelines
   8.      Appropriate Use Criteria
   9.      Public Comment
   10.      Health Disparities
   
   
4.      CMS Coverage Analysis
   
   1.      CMS Coverage Authority
   2.      CMS Analysis for Coverage of IPAPS for HF Management
      
      1.      Analysis of Key Evidence for CardioMEMS
         
      2.      Analysis of Key Evidence for Cordella
         
      3.      Conclusions
         
      4.      Rationale for Coverage Requirements for IPAPS for HF Management (Patient, Physician, and CED Study criteria)
         
      5.      Evidence Questions – Answered
   3.      Benefit Category
   4.      Patient Evaluation:
   5.      Shared-Decision Making


5.      History of Medicare Coverage
   
   1.      Current National Coverage Request
      
   2.      Timeline of NCA Milestones


6.      Appendices
   
   Appendix A: Proposed Medicare National Coverage Determinations Manual Language
   
   1.      Proposed Decision
      
   2.      Coverage Criteria
      
      1.      Patient Criteria
         
      2.      Physician Criteria
         
      3.      CED Study Criteria
         
   3.      Other Uses of IPAPS
      
   Appendix B. Referenced Materials
   
   Appendix C. New York Heart Association (NYHA) Functional Classification for Heart Failure
   
Bibliography

Abbreviations used throughout the Proposed Decision Memorandum for Implanted Pulmonary Artery Pressure Sensors for Heart Failure Management

ACC – American College of Cardiology
AHA – American Heart Association
APM - Alternative Payment Model
AUC – Area Under the Curve
AVR – Aortic Valve Replacement
BNP - B-type natriuretic peptide
CI – Confidence Interval
CMS – Centers for Medicare & Medicaid Services
CRT – Cardiac Resynchronization Therapy
DSRC – Device-Related or System-Related Complications
ESC – European Society of Cardiology
FDA – Food and Drug Administration
GDMT - Guideline-Directed Medical Therapy
HF – Heart Failure
HFH – Heart Failure Hospitalizations
HFpEF – Heart Failure with Preserved Ejection Fraction
HFmrEF – Heart Failure with Mid-Range Ejection Fraction
HFrEF – Heart Failure with Reduced Ejection Fraction
HFSA – Heart Failure Society of America
HR – Hazard Ratio
ICD - Implantable Cardioverter Defibrillator
IHM - Implantable Hemodynamic Monitoring
IPAPS – Implanted Pulmonary Artery Pressure Sensor(s)
IRR – Incidence Rates Ratio
KCCQ - Kansas City Cardiomyopathy Questionnaire
LVAD – Left Ventricular Assist Device
LVEF – Left Ventricular Ejection Fraction
MIPS - Merit-based Incentive Payment System
NCD – National Coverage Determination
NEJM – New England Journal of Medicine
NYHA – New York Heart Association
NT-proBNP - Aminoterminal pro B-type Natriuretic Peptide
PA – Pulmonary Artery
PAP – Pulmonary Artery Pressure
PAPS – Pulmonary Artery Pressure Sensor
PAS – Post Approval Study
PH - Pulmonary Hypertension
QoL – Quality of Life
QPP – Quality Payment Program
SDM – Shared Decision Making
RCT – Randomized Controlled Trial
TA – Technology Assessment
US – United States
WHO – World Health Organization

I. Proposed Decision

The Centers for Medicare & Medicaid Services (CMS) proposes to cover implantable pulmonary artery pressure sensor(s) (IPAPS) for heart failure (HF) management under Coverage with Evidence Development (CED) according to the provisions in sections (B) and (C) below.

We propose that implantation of an IPAPS is covered for HF management when furnished according to a Food and Drug Administration (FDA) market-authorized indication and all of the following conditions are met:

The patient meets all of the following criteria:

a)    Diagnosis of chronic HF of at least 3 months duration and in New York Heart Association (NYHA) functional Class II or III within the past 30 days, prior to PAPS implantation, regardless of left ventricular ejection fraction (LVEF).

b)   History of HF hospitalization or urgent HF visit (emergency room or other outpatient visit requiring intravenous diuretic therapy) within the past 12 months, or elevated natriuretic peptides within the past 30 days.

c)    On maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months prior to PAPS implantation.

d)   Evaluated for, and received if appropriate, an implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy (CRT)-Pacemaker (CRT-P), or CRT-Defibrillator (CRT-D). Implantation of the device must occur at least 3 months prior to PAPS implantation.

e)    No major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary intervention, open heart surgery, or stroke) within the last 3 months prior to PAPS implantation.

f)    Possessing adequate technology to ensure reliable remote connectivity to the IPAPS device.

g)   Must not have PAPS implantation occur during a hospital admission for an acute HF episode. 

The IPAPS items and services are furnished by practitioners who meet the following criteria, as applicable:

a)    Physicians referring Medicare patients and managing them post implantation must be cardiologists with experience in advanced HF management.

b)   Physicians implanting an IPAPS must have advanced training and experience in pulmonary arterial catheterization and intervention.

The IPAPS items and services are furnished in the context of a CMS-approved CED study. CMS-approved CED study protocols must: include only those patients who meet the criteria in section B.1; furnish items and services only through practitioners who meet the criteria in section B.2; and include all of the following:

a)    Primary outcomes of “HF hospitalization” (the cumulative number of HF hospital admissions, and HF emergency room or other outpatient visits requiring intravenous diuretics), all-cause mortality, or a composite of these, through a minimum of 24 months. Each component of a composite outcome must be individually reported.

b)   An active comparator.

c)    A care management plan that:

• Identifies members, roles and responsibilities of the physician-led HF clinical team (e.g., physicians, physician assistants, nurse practitioners, nurses) that performs the follow-up IPAPS patient monitoring and medication management; and
• Specifies the medication management protocols the patient and HF clinical team must follow.

d)   Design sufficient to demonstrate clinical utility of the IPAPS for HF management using direct measures of clinical behavior (e.g., counts of patient/physician interactions, counts and type of medication changes, counts of unscheduled outpatient clinic visits, counts of days within clinician set thresholds) to effectively manage and improve patient outcomes.

e)    Design sufficient for subgroup analyses by:

• CRT and/or ICD status (with/without);
• Age (75+ years);
• Sex;
• Race and ethnicity;
• LVEF (by guideline-defined subgroups);
• NYHA Class II vs III (as appropriate based on the FDA-approved label);
• Stage IV or greater chronic kidney disease;
• HF hospitalization in the past 12 months vs elevated natriuretic peptides alone in the last 30 days.

f)    In addition, CMS-approved CED studies must adhere to the scientific standards (criteria 1-17 below) that have been identified by the Agency for Healthcare Research and Quality (AHRQ) as set forth in Section VI. of CMS’ Coverage with Evidence Development Guidance Document, published August 7, 2024 (the “CED Guidance Document”).

1. Sponsor/Investigator:  The study is conducted by sponsors/investigators with the resources and skills to complete it successfully.
2. Milestones:  A written plan is in place that describes a detailed schedule for completion of key study milestones, including study initiation, enrollment progress, interim results reporting, and results reporting, to ensure timely completion of the CED process.
3. Study Protocol:  The CED study is registered with ClinicalTrials.gov and a complete final protocol, including the statistical analysis plan, is delivered to CMS prior to study initiation. The published protocol includes sufficient detail to allow a judgment of whether the study is fit-for-purpose and whether reasonable efforts will be taken to minimize the risk of bias.  Any changes to approved study protocols should be explained and publicly reported.
4. Study Context: The rationale for the study is supported by scientific evidence and study results are expected to fill the specified CMS-identified evidence deficiency and provide evidence sufficient to assess health outcomes.
5. Study Design:  The study design is selected to safely and efficiently generate valid evidence of health outcomes. The sponsors/investigators minimize the impact of confounding and biases on inferences through rigorous design and appropriate statistical techniques. If a contemporaneous comparison group is not included, this choice should be justified, and the sponsors/investigators discuss in detail how the design contributes useful information on issues such as durability or adverse event frequency that are not clearly answered in comparative studies.
6. Study Population: The study population reflects the demographic and clinical diversity among the Medicare beneficiaries who are the intended population of the intervention, particularly when there is good clinical or scientific reason to expect that the results observed in premarket studies might not be observed in older adults or subpopulations identified by other clinical or demographic factors. At a minimum, this includes attention to the intended population’s racial and ethnic backgrounds, gender, age, disabilities, important comorbidities, and, dependent on data availability, relevant health related social needs. For instance, more than half of Medicare beneficiaries are women so study designs should, as appropriate, consider the prevalence in women of the condition being studied as well as in the clinical trial and subsequent data reporting and analyses.
7. Subgroup Analyses: The study protocol explicitly discusses beneficiary subpopulations affected by the item or service under investigation, particularly traditionally unerrepresented groups in clinical studies, how the inclusion and exclusion requirements effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. In the protocol, the sponsors/investigators describe plans for analyzing demographic subpopulations as well as clinically-relevant subgroups as identified in existing evidence. Description of plans for exploratory analyses, as relevant subgroups emerge, are also included.
8. Care Setting: When feasible and appropriate for answering the CED question, data for the study should come from beneficiaries in their expected sites of care.
9. Health Outcomes: The primary health outcome(s) for the study are those important to patients and their caregivers and that are clinically meaningful. A validated surrogate outcome that reliably predicts these outcomes may be appropriate for some questions. Generally, when study sponsors propose using surrogate endpoints to measure outcomes, they should cite validation studies published in peer-reviewed journals to provide a rationale for assuming these endpoints predict the health outcomes of interest. The cited validation studies should be longitudinal and demonstrate a statistical association between the surrogate endpoint and the health outcomes it is thought to predict.
10. Objective Success Criteria:  In consultation with CMS and AHRQ, sponsors/investigators establish an evidentiary threshold for the primary health outcome(s) so as to demonstrate clinically meaningful differences with sufficient precision.
11. Data Quality:  The data are generated or selected with attention to provenance, bias, completeness, accuracy, sufficiency of duration of observation to demonstrate durability of health outcomes, and sufficiency of sample size as required by the question.
12. Construct Validity:  Sponsors/investigators provide information about the validity of drawing warranted conclusions about the study population, primary exposure(s) (intervention, control), health outcome measures, and core covariates when using either primary data collected for the study about individuals or proxies of the variables of interest, or existing (secondary) data about individuals or proxies of the variables of interest.
13. Sensitivity Analyses:  Sponsors/investigators will demonstrate robustness of results by conducting pre-specified sensitivity testing using alternative variable or model specifications as appropriate.
14. Reporting: Final results are provided to CMS and submitted for publication or reported in a publicly accessible manner within 12 months of the study’s primary completion date. Wherever possible, the study is submitted for peer review with the goal of publication using a reporting guideline appropriate for the study design and structured to enable replication. If peer-reviewed publication is not possible, results may also be published in an online publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials.gov, or in journals willing to publish in abbreviated format (e.g., for studies with incomplete results).
15. Sharing:  The sponsors/investigators commit to making study data publicly available by sharing data, methods, analytic code, and analytical output with CMS or with a CMS-approved third party. The study should comply with all applicable laws regarding subject privacy, including 45 CFR § 164.514 within the regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient Records.
16. Governance: The protocol describes the information governance and data security provisions that have been established to satisfy Federal security regulations issued pursuant to HIPAA and codified at 45 CFR Parts 160 and 164 (Subparts A & C), United States Department of Health and Human Services (HHS) regulations at 42 CFR, Part 2: Confidentiality of Substance Use Disorder Patient and HHS regulations at 45 CFR Part 46, regarding informed consent for clinical study involving human subjects. In addition to the requirements under 42 CFR and 45 CFR, studies that are subject to FDA regulation must also comply with regulations at 21 CFR Parts 50 and 56 regarding the protection of human subjects and institutional review boards, respectively.
17. Legal:  The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals, although it is acceptable for a study to test a reduction in toxicity of a product relative to standard of care or an appropriate comparator.  For studies that involve researching the safety and effectiveness of new drugs and biological products aimed at treating life-threatening or severely-debilitating diseases, refer to additional requirements set forth in 21 CFR § 312.81(a).

Consistent with section 1142 of the Act, AHRQ supports clinical research studies that CMS determines meet all the criteria and standards identified above.

All other uses of IPAPS are non-covered.

See Appendix A for proposed Medicare National Coverage Determinations Manual language.

CMS is seeking comments on our proposed decision.  We will respond to public comments in a final decision memorandum, as required by § 1862(l)(3) of the Act.

II. Clinical Review

Heart failure (HF) is a chronic syndrome in which the heart muscle cannot pump enough blood to meet the body’s needs. This results in protean symptoms, including fatigue and shortness of breath, and limits an individual’s ability to engage in everyday physical activities such as walking or climbing stairs.  As HF is the end-stage manifestation of most forms of heart disease, traditional cardiovascular risk factors also apply to HF, including age, diabetes, hypertension, hyperlipidemia, smoking, and obesity.  US and European diagnostic criteria for HF are summarized in a 2021 Circulation Research review (Roger 2021).  Generally, HF diagnosis is determined by patient symptoms (e.g., orthopnea, dyspnea on exertion) and objective signs (elevated venous pressure, pulmonary crackles or rales).  The American College of Cardiology (ACC), American Heart Association (AHA), and the Heart Failure Society of America (HFSA) published the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (Heidenreich 2022), which provides updated evidenced-based recommendations for clinicians to prevent, diagnose, and manage patients with HF. The European Society of Cardiology (ESC) published guidelines for the diagnosis and treatment of acute and chronic HF in 2021 (McDonagh 2021). Badger (2023) published a summary and comparison of the ACC/AHA/HFSA HF 2022 and ESC 2021 guidelines and reported minimal differences between the two. The authors highlighted some differences in HF staging and medication recommendations due to the difference between when the guidelines were published and the evidence considered for each. The ESC has released a focused update of their guidelines in 2023 (McDonagh 2023).

Although HF can be a result of right and/or left ventricular dysfunction, HF is often classified by left ventricular ejection fraction (LVEF or EF), a measure of the amount of blood volume pumped out of the heart with each contraction, to reflect HF patients’ differing prognosis and response to treatment.  HF patients may present with preserved LVEF, in Heart Failure with preserved Ejection Fraction (HFpEF), or with reduced LVEF, in Heart Failure with reduced Ejection Fraction (HFrEF). Both the AHA/ACC/HFSA and ESC guidelines also recognize an LVEF HF classification between the HFrEF and HFpEF range as HFmrEF, representing “HF with mid-range EF” or “HF with mildly reduced EF” (the latter used by AHA/ACC/HFSA). In HFpEF (LVEF > 50%), the muscles of the heart contract relatively normally, but heart muscle thickening and diastolic dysfunction may result in high left ventricular (LV) filling pressures despite normal or near normal LVEF. In HFrEF, LVEF is ≤40%, compared to normal LVEF ranges of 50-70% (Roger et al, 2021). HFmrEF patients may be diagnosed with an EF of 41% to 49%, patient signs and symptoms, and further objective measures (Heidenreich 2022, McDonagh 2023).

AHA/ACC/HFSA define stages of HF to emphasize the development and progression of HF (Heidenreich 2022).  HF is also classified by the severity of symptoms and functional capacity of patients with symptomatic or advanced HF. The most commonly used classification is the New York Heart Association (NYHA) Functional Classification system (Appendix C), based on clinician subjective evaluation of patient symptoms and corresponding physical activity limitation: I=asymptomatic and no limitation with ordinary activity; II= mild symptoms and slight limitations with ordinary activity; III= symptoms with minimal exertion, but comfortable at rest; IV=unable to engage in any physical activity without discomfort and symptoms even at rest. A patient’s classification may change dynamically over time, whether worsening or improving (e.g., a patient may improve from Class III to II due to optimal medical therapy and lifestyle changes). The NYHA classification system is commonly used in trials to select patients, and in clinical practice to determine eligibility for treatment strategies (Heidenreich 2022, McDonagh 2021).

Over 6.7 million Americans live with HF (Martin 2024).  A recent review of 20 years of National Health and Nutrition Examination Survey (NHANES) self-reported data, suggests HF prevalence in US adults varied between 1.9% to 2.6% (Bozkurt 2023, Siontis 2022).  The prevalence of HF is projected to increase by 46% from 2012 (when HF hospitalizations began to increase) to 2030, affecting > 8 million adults (Bozkurt 2023, Martin 2024).

Prevalence of HF is 4 times higher among adults over 65 years old than those younger than 65 years (Bozkurt 2023, Roger 2021).  Thus, HF is a substantial burden for the Medicare population.  Nearly all Medicare beneficiaries with HF have significant comorbidities, as seen in Figure A below.

Figure A: Top Chronic Conditions Among Medicare Beneficiaries

Source: Derived from fee-for-service claims data from the CMS Chronic Conditions Wearhouse

Lifetime risk of HF is elevated with higher blood pressure and body mass index at all ages (Bhambhani 2018, Tsao 2018).  NHANES data highlight that one-third of US adults have at least 1 HF risk factor, with a population attributable risk for incident HF estimated to be 52% attributed to four key factors: hypertension, diabetes, obesity, and smoking (Martin 2024).

Overall, mortality due to HF remains high at approximately 50% at 5 years (Roger 2021). Risk stratification models continue to evolve.  A 2021 study suggested that 6 comorbidity phenotypes (CHD, valvular heart disease, atrial fibrillation, sleep apnea, chronic obstructive pulmonary disease, minimal comorbidities) may stratify all-cause death or hospital readmissions with greater discrimination than LVEF categories (Gevaert 2021). 

The 2022 AHA/ACC/HFSA HF guideline recommends screening for and managing HF risk factors and comorbid conditions and includes recommendations for lifestyle modification (Heidenreich 2022).  Physicians are advised to assess HF patients for early signs of hemodynamic congestion, which is associated with poor quality of life (QoL) and prognosis (Heidenreich 2022).  Most HF hospitalizations result from a gradual increase in cardiac filling pressures rather than from sudden decompensation (Heidenreich 2022).  Precipitating factors can often be identified, such as acute coronary syndrome, uncontrolled hypertension, atrial fibrillation and other arrhythmias, additional cardiac disease (e.g., endocarditis), acute infections (e.g., pneumonia, urinary tract), and nonadherence to medication regimes or dietary intake (Heidenreich 2022).  Preventing the worsening of HF symptoms and prognosis is a major target of current HF treatment and the subject of a recent clinical consensus statement by the Heart Failure Association of the European Society of Cardiology (Metra 2023).  Decompensation events leading to HF hospitalizations are associated with poor long-term outcomes (Gheorghiade 2006, Tu 2009, Setoguchi 2007).  Suboptimal inpatient management of decompensated HF often results in persistent congestion upon hospital discharge and subsequent increased risk of recurrent hospitalization, morbidity, and mortality (Chapman 2019).

Several strategies exist for remote monitoring and management of HF.  Many studies, but not all, have found that multidisciplinary, nurse-led HF disease management programs with close follow-up improve health outcomes.  In meta-analyses, case management has been shown to reduce the odds of HF hospitalization by 53% and mortality by 34%.  More recently, the STRONG-HF trial demonstrated the value of an intensive treatment strategy with rapid up-titration of guideline-directed medication and close follow-up after an acute heart failure admission compared with usual care in improving symptoms, improving patient quality of life, and reducing the risk of 180-day all-cause death or HF readmission (Mebazaa 2022).  Up-titration in the high-intensity care group was achieved by using more early outpatient clinic visits than in the usual care group (4.8 vs. 1.0).

Meta-analyses of small telemonitoring studies demonstrated a reduction in all-cause mortality and HF hospitalizations with telemonitoring (Inglis 2010).  However, there was marked heterogeneity in the populations and interventions studied, along with methodological limitations: small sample sizes, unblinded reviewers, or single-center settings.  Large clinical trials have had mixed results.  The TEN-HMS trial showed a significant reduction in 1-year mortality with either home telemonitoring or nurse telephone support compared with usual care. However, the Tele-HF and TIM-HF trials failed to demonstrate significant clinical benefit with telemonitoring (Chaudhry 2010, Cleland 2005, Koehler 2011).

The Interdisciplinary Network Heart Failure (INH) Trial (715 patients, 2004-2007) did not show a benefit with remote monitoring for the primary endpoint of time to all-cause death or rehospitalization in patients after acute decompensation for systolic HF compared with usual care at 6 months.  On exploratory analysis, HF hospitalizations were actually higher in the remote monitoring group but mortality and QoL measures (NYHA class) were improved (Angermann 2012).  The E-INH trial added more patients (1,032 patients, 2004-2008) and followed them for up to 120 months, testing multiple time points.  There appeared to be a mortality benefit between 60-120 months but no difference in HF hospitalizations or death was noted at 60 months.  The trial is challenging to interpret due to limitations of study design and the time period when patients were enrolled (2004-2008).  Since then, there have been important advances in GDMT for HF management.

A large proportion of HF patients receive implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT), and these devices can also be used for remote evaluation using heart rate variability, patient activity, and intrathoracic impedance.  The intrathoracic impedance, measured between the right ventricular lead and the generator, decreases with pulmonary edema and inversely correlates with the pulmonary capillary wedge pressure (Yu 2005).  However, trials evaluating the use of implanted device data, including intrathoracic impedance, have not consistently demonstrated an improvement in clinical outcomes (Bohm 2016, Boriani 2017, Hindricks 2014, Morgan 2017, van Veldhuisen 2011).

The standard of care for monitoring fluid status in chronic HF in the outpatient setting involves monitoring changes in HF signs and symptoms, including increasing dyspnea, changes in body weight and blood pressure (Heidenreich 2022, McDonagh 2021).  Studies monitoring cardiac pressures in HF populations demonstrate that patients hospitalized for volume overload typically have higher baseline cardiac pressures and experience further pressure increases days to weeks prior to hospitalization.  Hemodynamic changes (changes in blood flow in vessels) are detectable up to 2 weeks prior to the onset of symptoms or weight gain (Boriani 2017).  As a result, supplemental monitoring strategies have been explored.  However, significant variability in PAP during a 24-hour period is known to occur so that the clinical trigger for action in an individual patient cannot be known with certainty and, similarly, appropriate frequency of monitoring is unknown.

Remote hemodynamic monitoring via an IPAPS system is designed to allow healthcare providers to noninvasively monitor PA pressures in the outpatient setting (Ayyadurai 2019).  The intent is for physicians to use the trended hemodynamic data to remotely control PA pressures of HF patients at home through responsive medication management, with the goal of reducing HF hospitalizations. 

Given the many options for remote monitoring and the variable outcomes reported in the literature, evidence remains in a state of equipoise with respect to intensive tele-management approaches to heart failure.

The FDA has market authorized two IPAPS systems for HF management: CardioMEMS (Abbott Medical) and Cordella (Edwards Lifesciences).

On May 28, 2014, the FDA initially market authorized the CardioMEMS Heart Failure Pressure Measurement System, and on February 18, 2022, the FDA expanded the indication to the following:

“The device is indicated for wirelessly measuring and monitoring pulmonary artery pressure and heart rate in NYHA Class II or III heart failure patients who either have been hospitalized for heart failure in the previous year and/or have elevated natriuretic peptides.  The hemodynamic data are used by physicians for heart failure management with the goal of controlling pulmonary artery pressures and reducing heart failure hospitalizations.”  https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100045S056

The CardioMEMS HF System consists of a wireless sensor, a patient electronics system, and a secured patient database for clinician review.  The wireless sensor, which is permanently implanted into the distal left pulmonary artery (PA), is a patented microelectromechanical system (MEMS) that consists of a metallic coil that serves as an antenna and a pressure sensitive capacitor fused between two hermetically sealed wafers.  Pressure on the capacitor alters the resonant frequency of the externally emitted radiofrequency energy in a linear relationship which is detected by the external antenna.  This allows the sensor to function using externally transmitted energy rather than an implanted lead or battery (Ayyadurai 2019).  Implanting the sensor is an approximately one-hour, catheter-based procedure.

Once implanted, the wireless sensor provides noninvasive hemodynamic data that are transmitted by the patient to an online secured database.  Patients transmit this data through their home electronics unit which includes a monitor, wand, and a pillow with sensory capabilities to power and interrogate the device.  Physicians instruct patients on how frequently they should take a reading.  To take and transmit a PA pressure reading requires approximately two to three minutes. To take a reading, patients position the antenna (preassembled in a pillow) on a flat surface four to five feet away from the home electronics unit, turn on the unit using the power button located on the back of the unit and lay on the pillow.  Throughout the process the home electronics unit uses audible prompts to guide patients.  To initiate a PA pressure reading, patients press a button on a small remote connected to the home electronics unit with a wire.  When patients initiate a reading, the electronics unit assesses the signal strength between the sensor and the antenna.

The home electronics unit uses a USB cellular adapter, wi-fi, or landline to transmit the PA pressure information to a secure website and then automatically turns off.  The online secured database provides data to the clinician and care team, including alerts sent to the physician based upon outputs programmed and tailored for the individual patient.  In general, the goal is for patients to upload every day and have qualified healthcare provider review weekly.  If PA pressure is not opti-volemic, monitoring may be more frequent.

On June 20, 2024, the FDA market authorized the Cordella Pulmonary Artery Sensor System with the following indication:

“The Cordella Pulmonary Artery Sensor System is intended to measure, record and transmit pulmonary artery pressure (PAP) data from NYHA Class III heart failure patients who are at home on diuretics and guideline-directed medical therapy (GDMT) as well as have been stable for 30 days on GDMT.  The device output is meant to aid clinicians in the assessment and management of heart failure, with the goal of reducing heart failure hospitalizations.” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P230040

The Cordella PA Sensor is an implantable blood pressure monitor that permanently resides in the patient’s right pulmonary artery.  The Cordella PA Sensor System interfaces with the commercial Cordella HF System to facilitate pulmonary artery pressure (PAP) readings at a patient’s home and transmission of the results to a care provider for evaluation. The Cordella HF System is a kit with Bluetooth connected off-the-shelf peripherals (for monitoring vital signs), myCordella Tablet (running the myCordella Patient App), and the myCordella Patient Management Portal (PMP), that interfaces with the Cordella PA Sensor System.  Once home, the patient holds a wireless handheld sensor on their right chest to transmit PA pressure readings.  The Cordella device is also designed to measure and transmit vital signs, including blood pressure, heart rate, weight, and oxygen saturations (Mullins 2020).

III. Evidence

This section provides a summary of the evidence that includes peer-reviewed publications of pertinent clinical studies on IPAPS for HF management and evidence-based guidelines which we considered in our coverage analysis (See Section IV. B.).  This NCA does not address external fluid retention sensors or inpatient invasive PA pressure measurement.

A detailed account of the methodological principles of study design that CMS uses to assess the relevant literature may be found in the CMS National Coverage Analysis Evidence Review Guidance Document, published August 7, 2024, or any successor document (the “Evidence Review Guidance Document”).

The following questions guided our clinical literature search, review, and analysis of the evidence on IPAPS for HF management.  We answer these questions in Section IV.B.5. following the CMS coverage analysis.

Q1.  Is the evidence sufficient to conclude that use of IPAPS for HF management meaningfully improves health outcomes for Medicare beneficiaries?

Q2.  Do specific characteristics or comorbidities make patients more or less likely to benefit from the use of IPAPS for HF management?

Q3.  Are specific treatment conditions necessary to achieve outcomes with the use of IPAPS for HF management similar to those demonstrated in the clinical studies reviewed in this analysis?

CMS did not request an external technology assessment (TA) on this issue.  Our review did not identify Cochrane or Evidence-based Practice Center (EPC) reviews of these devices. 

A MEDCAC meeting was not convened on IPAPS for HF management. 

Our initial literature search identified, for CardioMEMS (Abbott), three randomized controlled trials (RCTs) (one of which was reported in two separate publications), nine observational studies (five prospective, single-arm studies and eight retrospective studies), 14 subsequent analyses of prospectively collected data (pre-specified or post-hoc), and four meta-analyses.  All reports included patient populations with NYHA Class II or III HF who were followed for 6-48 months.  Additionally, we reviewed the published literature for another device in this class, Cordella (Edwards Lifesciences).  The reviewed studies are summarized in Table 1 (all studies are for CardioMEMS unless otherwise noted).  See References for studies referred to in this NCD analysis.  We used contractor support to conduct the literature searches and evidence review, and supplemented that review with our own CMS coverage analysis.  Additional papers are considered as they come to our attention, including in public comment periods.  This process is similar to the Evidence Preview concept discussed in the Processes and Procedures for the TCET Pathway document. (89 Fed. Reg. 65750, Aug. 12, 2024).

CMS, with contractor support, performed a literature search of PubMed and Embase with the following primary search terms: (1) “cardiomems”, (2) “blood pressure monitoring”, (3) “hemodynamic monitoring”, or (4) “pulmonary artery pressure monitoring”; AND (5) “heart failure” (see Search Strategy for complete list of terms used).  The search included published English language medical literature from January 01, 2004 – December 15, 2022 for remote IPAPS for HF (CardioMEMS HF System).  An updated literature search was performed on February 13, 2024, to identify articles published between December 2022 and February 2024.  The search terms and search strategy used in the update search are provided in Appendix B.

The literature search focused on the CardioMEMS HF System for NYHA Class II or III HF, population risk factors, and endpoints.  It excluded research reports with fewer than 100 patients, editorials, and conference abstracts.  Complete inclusion and exclusion criteria are described in Appendix B.

The original search identified a total of 1285 publications, 25 of which met inclusion criteria.  For the articles not included in the review, the reasons for exclusion were that the article was: clearly off topic, publication type not of interest, population not of interest, intervention not of interest, outcomes not of interest, or studies with <100 patients.

An updated literature search identified 393 additional citations, and resulted in the addition of 9 studies (See References).  IPAPS-relevant studies not included in this review are listed in Appendix B.  Additional relevant studies are considered as they come to our attention, to include through public comment periods.

CMS, with contractor support, conducted a literature search in PubMed and Embase on July 12, 2024, to retrieve relevant references using a combination of medical subject headings and keywords along with their synonyms and Boolean operators, the search targeted the terms “blood pressure monitoring” or “hemodynamic monitoring,” and “pulmonary artery pressure,” “heart failure,” or “Cordella.”  When inclusion and exclusion criteria matched those used for CardioMEMS, the search yielded no results.  A more expanded search was thus conducted to better assess the state of the published evidence as it exists.  Since completion of the initial search, the PROACTIVE-HF study was published (Guichard 2024) and was considered in the evidence review and CMS coverage analysis.

Table 1 Legend:
AE = adverse event; HFH = heart failure hospitalization; NP = elevated natriuretic peptides; MAUDE = Manufacturer and User Facility Device Experience; NYHA = New York Heart; Association; PAS = post approval study; RCT = randomized controlled trial; mo = month; yr = year; NR = not reported.
6MWT = 6-minute walk test; DSRC = device or system-related complications; EQ-5D-5L = EuroQuol 5-dimension, 5-level instrument; KCCQ = Kansas City Cardiomyopathy Questionnaire; MLWHFQ = Minnesota Living With Heart Failure Questionnaire; MPAP = mean pulmonary artery pressure; QoL = quality of life; PH = Pulmonary hypertension; IpcPH = isolated post-capillary PH; CpcPH = combined post- and pre-capillary PH.

Only significant results are designated by an asterisk *p<0.05; **p<0.01; ***p<0.001; all data reported as “device; control” unless otherwise specified.

The assessment considered randomized controlled trials and meta-analyses, as well as prospective single-arm and retrospective observational studies, and prespecified or post-hoc subgroup analyses of collected data.  We summarize the studies below.

The three CardioMEMS randomized trials were:

• CHAMPION (Abraham 2011, 2016)
• GUIDE-HF (Lindenfeld 2021)
• MONITOR-HF (Brugts 2023)

The PROACTIVE-HF study (Guichard 2024) assessed outcomes using a newer IPAPS device, Cordella.

CHAMPION was conducted at 64 sites in the US, GUIDE-HF took place at 118 sites in the US and Canada, and MONITOR-HF enrolled patients at 25 sites in the Netherlands.  Surgical implantation of the PA pressure sensors for both the CHAMPION and GUIDE-HF trials took place in an inpatient hospital setting.  All patients in each trial took daily pressure readings at home and at study follow-up visits, along with PA pressure guided HF management.

Baseline characteristics of participants in the CardioMEMS RCTs are provided in Table 3.

Table 3.  Comparison of baseline patient characteristics in the CardioMEMS RCTs

Legend: BP = blood pressure; LVEF = left ventricular ejection fraction; mmHg = millimeters of mercury; MPAP = mean pulmonary artery pressure; NYHA = New York Heart Association

Study Endpoints
The three CardioMEMS RCTs varied in the endpoints investigated.  CHAMPION’s focus was the rate of HF hospitalizations.  GUIDE-HF evaluated a composite of all-cause mortality and total HF events (HF hospitalizations and urgent HF hospital visits).  The primary efficacy endpoint for MONITOR-HF was a change in the Kansas City Cardiomyopathy Questionnaire overall summary scores from baseline to 12 months between groups, with a secondary endpoint looking at total number of HF hospitalizations and urgent visits requiring intravenous diuretics during follow-up.  CHAMPION and MONITOR-HF enrolled only NYHA class III patients, while GUIDE-HF also enrolled class II and a few class IV patients.  In PROACTIVE-HF (for Cordella) the primary efficacy endpoint was the 6-month incidence of the composite of HF hospitalization or all-cause mortality compared with a performance goal derived from prior trials.  Key secondary outcomes included number of HF hospitalizations at 6 months postimplant compared with 6 months prior to implant; all-cause mortality; change from baseline of PA pressure, quality of life, and functional capacity; and patient and site adherence to PA pressure monitoring and medication changes.

CHAMPION
Compared to the control group, the treatment group had a 33% reduction in annualized HF hospitalization rates during the initial period.  A relative risk reduction of 33% for a hard clinical outcome such as HF hospitalization has been presented in the medical literature as being clinically significant, as HF hospitalization represents a particularly morbid outcome that results in marked loss of quality of life and is associated with increased mortality (Vaduganathan 2022, Shah 2017).  The magnitude of clinical benefit is similar to the effect of empagliflozin on HF hospitalization in HFrEF (31% relative risk reduction; Packer 2020).  After uploaded PA pressure data became available to guide therapy during the open access period, annualized rates of HF hospitalizations were reduced in the former control group by 48% (0.36 vs. 0.68; HR: 0.52 [95% CI 0.40 to 0.69]; p<0.0001) compared with HF hospitalizations in the control group during the randomized period.  During the randomized period, the treatment group saw significant improvements in measurements of QOL (Minnesota Living With Heart Failure Questionnaire 45 vs. 51; p=0.02) and PA pressures (AUC -156 vs. 33 mmHg-days; p=0.008) compared to the control group.  Mortality rates did not differ between the treatment group and controls across the entire follow-up period.  As for safety measures, significant adverse events (AEs) reported in the initial 6-month randomized period were rare (0.7%) and no further AEs or device failures were reported during the open access period.

GUIDE-HF
Patients were enrolled and followed up before and during the COVID-19 pandemic.  Prior to COVID-19, the treatment group had lower annualized primary endpoint event (mortality, HF hospitalization and urgent HF hospital visit) rates compared to the control group (0.553 vs. 0.682; HR: 0.81, 95% CI 0.66 to 1.00; p=0.049).  Similarly, prior to COVID-19, annualized HF hospitalization rates were reduced in the treatment group compared to the control group (0.38 vs. 0.525; HR: 0.72, 95% CI 0.57 to 0.92; p=0.0072).  The HF hospitalization relative risk reduction of 28% is similar in magnitude to the results of the CHAMPION trial and were clinically significant.  In the overall analysis, including follow-up that occurred after the start of the pandemic, these efficacy findings were no longer significant.  Serious AEs occurred in 57% of patients in the treatment arm and 53% of patients in the control arm, but specific AEs were not described.  Further investigation revealed that disease severity, based on hemodynamic assessment, improved in both groups during the time that HF events decreased.  Data showed that PA pressures decreased in both groups, despite a reduction in the intensity of medical management (number of provider-prescribed medication changes) in both groups.

MONITOR-HF
The trial design was similar to the other two RCTs but was the first to investigate the efficacy, safety, and benefits of pulmonary-artery-pressure-guided HF management in a European health-care system (the Netherlands).  Unlike the other two RCTs in which all patients received the device, participants were randomly allocated to either PAP-guided management with the CardioMEMS device or a no-implant, standard HF care group.  As in CHAMPION, all patients enrolled in MONITOR-HF were classified as NYHA class III and not excluded or stratified into groups by LVEF.  The researchers chose a QOL outcome (KCCQ) as the primary efficacy endpoint (between group summary scores from baseline to 12 months).  Analysis of the KCCQ scores demonstrated significant differences in the mean change at 12 months between groups (p=0.013) and within the CardioMEMS treatment group (p=0.0014).  Results favored the CardioMEMS group (improvement OR: 1.69, 95% CI 1.01 to 2.83; p=0.046; deterioration OR: 0.45, 95% CI 0.26 to 0.77; p=0.0035).  Secondary outcomes for HF hospitalization also favored the device treatment group, with 44% reduction in the rate of total HF hospitalizations (HR: 0.56, 95% CI 0.38 to 0.84; p=0.0053) compared to the control group.  Patients did experience a significant reduction in pulmonary artery pressure at the 12-month follow-up (p<0.0001).  The median NT-proBNP was significantly reduced at 12 months in the CardioMEMS device group (p=0.013) but not in the standard care group (p=0.81).  No significant difference in cardiovascular (HR: 0.83, 0.49 to 1.39; p=0.485) or all-cause death (HR: 0.96, 0.63 to 1.46, p=0.846) was observed.  The freedom of device-related or system-related complications and sensor failure were 97.7% and 98.8%, respectively.  Finally, the mean number of patient contacts per month was higher in the CardioMEMS group compared to the control group during the entire follow-up period (1.55 vs. 1.04, significance not reported) and the cumulative number of changes, intensifications, and downgrades in diuretics and GDMT were higher in the CardioMEMS group than in the control group.  Considering significant results for all major study outcomes in favor of the CardioMEMS group (except death event rates), the authors conclude that findings support the use of the CardioMEMS HF system in the management of NYHA Class III HF patients.  They also present these findings in the context of a high rate of optimal, current GDMT for patients with HFrEF in both groups.

PROACTIVE-HF
The PROACTIVE-HF study, initially approved in 2018, was a prospective, randomized, controlled, single-blind, multicenter trial designed to evaluate the safety and effectiveness of the Cordella PA Pressure Sensor in patients with HF and NYHA functional class III symptoms.  Following its inception, as more clinical evidence for PAP-guided HF management emerged, the manufacturer perceived a challenge in maintaining clinical equipoise and enrolling patients into a standard-of-care control arm.  Consequently, after consultation with the FDA, the study design was changed in 2021 from a randomized controlled trial to a single-arm observational study, with prespecified safety and effectiveness endpoints aimed at demonstrating a similar risk/benefit profile to the CardioMEMS HF System.  The recently published report of this single-arm observational study found that for the 456 patients who were successfully implanted, the 6-month event rate for the primary composite outcome of HF hospitalization or all-cause mortality was 0.15 (95% CI: 0.12-0.20) which was significantly lower than the performance goal (0.15 vs 0.43; P < 0.0001).

RCT Study Quality

The RCTs were rated as low or some concern in terms of risk for bias using the Cochrane Rob2 risk-of-bias tool for randomized trials (Sterne 2019).  The main limitations of the RCTs’ study quality were related to risk of bias, which reduced confidence in the strength of the evidence.  The RCTs lacked blinding of the clinicians, something not uncommon in medical device studies.  An analysis of the CHAMPION quality must also include mention of a report on the 2011 FDA PMA decision (Loh 2013) which indicated controversies involving both the trial conduct and statistical analysis of efficacy endpoints in the CHAMPION trial.  This report detailed that although the pre-specified statistical model used by the investigators showed a highly significant treatment effect (p=0.0002), the results were no longer statistically significant when alternative statistical models were used to correct for over-dispersion.  Furthermore, this report identified evidence that study investigators had input into the treatment of some patients in the treatment arm, but not the control arm, introducing a significant risk of bias.  The MONITOR-HF study was an open-label, unmasked design.  This risk of bias was somewhat mitigated in GUIDE-HF.  While investigators in the GUIDE-HF trial were not blinded, communication to the patients was delivered by trial personnel who were unaware of the patient’s assigned study arm and using scripted language.

Meta-Analyses

Four meta-analyses were assessed in the initial evidence review, with considerable overlap between them and the studies already included in this review, and with complete overlap of relevant RCTs between them.  The meta-analyses were adequately designed, had pre-specified criteria, followed acceptable methodical approaches, and offered the benefit of pooled data as well as systematic assessments across studies.  Reported findings should be interpreted with the understanding that the analyses included multiple devices and patient populations that were broader than the current CardioMEMS FDA-labeled indications and not fully representative of outcomes expected with on-label use. The four meta-analyses are discussed below.

1. Laconelli (2022) reported results from a comprehensive systematic review and meta-analysis of RCTs comparing device-based remote monitoring strategies for congestion-guided HF management versus standard therapy.  The review included, but was not limited to, implanted hemodynamic monitoring devices.  Hemodynamic-guided HF management significantly reduced HFH but did not have a significant impact on mortality rates over 12 months of follow-up.  The authors concluded that hemodynamic-guided HF management is associated with better clinical outcomes as compared to standard clinical care.

2. Zito (2022) reported results from a comprehensive systematic review and meta-analysis of eight RCTs comparing device-based remote monitoring strategies for congestion-guided HF management versus standard therapy.  The review included implanted hemodynamic-monitoring devices and impedance-monitoring devices.  Hemodynamic-guided HF management significantly reduced HFH but did not have a significant impact on mortality rates over 12 months off follow-up.  The authors concluded that hemodynamic monitoring may reduce the risk of HFH but not mortality rates.

3. A systematic review and meta-analysis by Clephas (2023) included prospective RCTs (n > 100) comparing CardioMEMS device with a control group that reported HF-related clinical endpoints.  Total HF hospitalizations were lower across the trials’ PAP monitoring groups versus control standard of care without PAP implants. The analysis did not show a benefit to all-cause mortality but none of the studies were powered to detect an effect on mortality.  Multiple subgroup analyses favored the PA pressure monitoring groups.

4. Lindenfeld (2024) conducted a meta-analysis examining whether management with implantable hemodynamic monitors reduces mortality in patients with HF and HFrEF.  The authors also sought to confirm the effect of hemodynamic-monitoring guided management on HF hospitalization eduction reported in previous studies.  The analysis included patient-level pooled data for 1,350 patients with HFrEF (25.3% Female; 71% White) from two randomized studies of implantable hemodynamic PA pressure (CardioMEMS sensor; GUIDE-HF, CHAMPION) and a randomized study that used a left atrial pressure monitoring device (HeartPOD LAP sensor; LAPTOP-HF).  There were not enough patients with HFpEF for the researchers to evaluate mortality beyond 1 year of follow-up.  Patients were NYHA functional class II-IV (only 2.3% were class IV) with prior HF hospitalization or elevated natriuretic peptides.  Results indicated hemodynamic-monitoring guided management significantly reduced overall mortality at two years and a significant reduction in HF hospitalizations at one.  Due to the duration of study designs, the onset of COVID-19 (GUIDE-HF), and the LAPTOP-HF study early termination due to implant-related complications, the pooled data set was truncated to 12 months of follow-up for recurrent HFH analyses and at 24 months of follow-up for survival analyses.  The reduction in HF hospitalizations was seen early in the first year of monitoring and mortality benefits occur after the first year.  All three trials were conducted before updated guideline recommendations for sodium-glucose cotransporter-2 inhibitors and the availability of angiotensin receptor neprilysin inhibitor sacubitril/valsartan for CHAMPION and LAPTOP-HF. Finally, limitations also include the fact that GUIDE-HF and CHAMPION were single-blinded and LAPTOP-HF was unblinded with patient visibility of the LAP sensor.

Two additional, recently published meta-analyses surfaced after the initial literature review, and are discussed further in IV.B. CMS Analysis for Coverage of IPAPS for HF Management subsection. Curtain (2023) examined the effectiveness of IHM [implantable haemodynamic monitoring]-guided care across a range of ejection fractions (EFs), combining data from the five randomised trials [2710 patients] that investigated IHM-guided treatment, including a pre-COVID-19 sensitivity analysis from the recent Hemodynamic-Guided Management of Heart Failure (GUIDE-HF) trial.” In the overall population, “regardless of EF, IHM-guided care reduced total HF hospitalisations and total worsening HF events.” These positive results were driven by the HFrEF subgroup. The study found no reduction in mortality. The authors believed that “future trials should focus on people with an EF of =50% [the HFpEF subgroup] with pre-specified analyses to confirm the effectiveness of IHM-guided care in this population” (Curtain 2023).

Urban (2024) included five trials in its meta-analysis, the three recent ones for CardioMEMS, and two much older ones (published in 2008 and 2011 respectively), using the device Chronicle, for a total of 2,572 trial participants. The authors found that IPAP monitoring significantly reduced HF-related hospitalizations and HF events, with no impact on all-cause or cardiovascular mortality. “Subgroup analyses highlighted the significance of CardioMEMS and blinded studies.” One could criticize the inclusion of the much older studies which used a different device and different background optimal medical therapy, but we believe certain insights may help inform design considerations for CED studies, as we discuss further in our IV.B. CMS Analysis for Coverage of IPAPS for HF Management subsection.

The evidence reviewed for CardioMEMS and Cordella had important limitations of evidence that pertain to both devices (except where noted).  Further discussed in Section IV., these limitations of evidence represent evidence gaps that would need to be filled before Medicare could cover IPAPS for HF management under § 1861(a)(1)(A) of the Social Security Act.

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