National Coverage Analysis (NCA) Proposed Decision Memo

Implantable Pulmonary Artery Pressure Sensors for Heart Failure Management

CAG-00466N

Expand All | Collapse All

Decision Summary

The Centers for Medicare & Medicaid Services (CMS) covers 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.

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 guideline-directed medical therapy (GDMT) for at least 3 months with the goal of achieving optimal or maximally-tolerated GDMT 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)       Have access to reliable connectivity to ensure daily collection and submission of IPAPS data.

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 training and experience in HF management.

b)      Physicians implanting an IPAPS must have 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-P, CRT-D, or ICD (with hemodynamic monitoring capabilities) 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)       CMS-approved CED studies must adhere to the following 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 Opens in a new window, 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 underrepresented 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.

1.      IPAPS for HF management is not covered for patients outside of a CMS-approved study.

2.      Nothing in this NCD would preclude coverage of IPAPS for HF management through NCD 310.1 (Clinical Trial Policy) or through the Investigational Device Exemption (IDE) Policy.

See Appendix A for Medicare National Coverage Determinations Manual language.

Proposed Decision Memo

Table of Contents

  1.      Decision
    1.       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
      1. General support for IPAPS for HF management
      2. General support for Medicare Coverage for IPAPS for HF management
      3. Concerns about Coverage for IPAPS for HF management
      4. Coverage Policy – Device Criteria (FDA indication)
      5. Coverage Policy – Patient Criteria.
      6. Coverage Policy – Physician Criteria.
      7. CED for IPAPS for HF Management Generally.
      8. CED Criteria for IPAPS for HF Management
      9. Other Uses of IPAPS.
      10. Health Disparities/Accessibility.
      11. Miscellaneous Comments.
    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
    1.      Decision
    2.      Coverage Criteria
      1.      Patient Criteria
      2.      Physician Criteria
      3.      CED Study Criteria
    3.      Other Uses of IPAPS
  7. Bibliography Opens in a new window

Abbreviations used throughout the Decision Memorandum for Implantable 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 - Amino-terminal 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.                 Decision

The Centers for Medicare & Medicaid Services (CMS) covers 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.

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 guideline-directed medical therapy (GDMT) for at least 3 months with the goal of achieving optimal or maximally-tolerated GDMT 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)       Have access to reliable connectivity to ensure daily collection and submission of IPAPS data.

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 training and experience in HF management.

b)      Physicians implanting an IPAPS must have 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-P, CRT-D, or ICD (with hemodynamic monitoring capabilities) 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)       CMS-approved CED studies must adhere to the following 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 Opens in a new window, 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 underrepresented 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.

1.      IPAPS for HF management is not covered for patients outside of a CMS-approved study.

2.      Nothing in this NCD would preclude coverage of IPAPS for HF management through NCD 310.1 (Clinical Trial Policy) or through the Investigational Device Exemption (IDE) Policy.

See Appendix A for Medicare National Coverage Determinations Manual language.

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 Warehouse 

Lifetime risk of HF is elevated with higher blood pressure and body mass index (Bhambhani 2018, Tsao 2018). NHANES data highlight that one-third of US adults have at least one 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, and 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, and 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 Opens in a new window

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 Opens in a new window

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 Opens in a new window, 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 Opens in a new window 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 were considered as they came 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. Key Studies for IPAPS for Heart Failure Management
Study

Patients   Outcomes
# Author Year Study Design Inclusion (n) Age (yr) Male (%) Follow-up HFH
(annualized rate)
Mortality
(%)
QoL
(∆ from baseline)
∆ MPAP
(mmHg x days)
Freedom from Device Related or System Related Complications
(DSRCs)
(%)
Randomized Control Trials
1 Abraham et al.
(CHAMPION)

Abraham et al.
(Long term follow up of CHAMPION)
2011
2016
RCT NYHA III 270; 280 61.3; 61.8 72.0; 73.0 6 mo.
18 mo.
0.46; 0.68***
Former treatment: 0.45; 0.46
Former control: 0.36; 0.68***(open access vs. randomized access)
19.0; 23.0
Former treatment:18.0; 19.0
Former control: 12.0; 23.0
(open access vs. randomized access)
MLWHFQ
45±26; 51±25*
MLWHFQ

47.0; 56.5*
-156; 33**
NR
98.6
2 Lindenfeld et al.
(GUIDE-HF)
2021 RCT NYHA II-IV 497; 503 71; 70 62.0; 63.0 12 mo.

0.410; 0.497

Pre-COVID: 0.380; 0.525**

8.0; 7.4

Pre-COVID: 6.0; 4.97

KCCQ
5.20±22.5;
4.12±22.5
EQ-5D-5L
0.94±20.2;
2.90±20.7
6MWT
-12.8±100.1;
-6.46±106.6

Pre-COVID:
KCCQ
4.19±18.3;
5.05±22.1
EQ-5D-5L
-1.28±20.2;
3.89±17.7*
6MWT
-19.5±87.6;

-9.78±112.7

-792.7;
-582.9*

Pre-COVID:
-518.0;
-324.2*
99.2
3 Brugts
(MONITOR-HF)
2023 RCT NYHA III 176; 172 69; 70 78.4; 72.7 48 mo. 63 (0.254); 85 (0.395); HR 0.67 (0.49-0.93) * Rate/patient/year: 0.131, 0.144 KCCQ
7.05 ±4.28**;
–0.08 ±3.68
EQ-5D-5L
6.0±4.9*
6MWT
29.3m±26.9*; 9.8m±30.3
–1623.8 97.7
Prospective single-arm studies
4 Shavelle (US PAS) 2020 Prospective, single-arm NYHA III 1200 69 62.3

12 mo.

0.54; 1.25***

(1 year post- vs. 1 year pre- implant)

16.1 NR -790.9*** 99.6
5 Angermann (MEMS-HF) 2020 Prospective, single-arm NYHA III 234 67.9 78.2 12 mo.

0.27; 1.52***

(1 year post- vs. 1 year pre- implant)

13.8 KCCQ
12.7±1.6***
EQ-5D-5L
6.1±5.6***
NYHA ≥ 1 class improvement:
35.5%
-1827.7*** 98.3
6 Cowie
(COAST-UK)
2022 Prospective, single-arm NYHA III 100 69 70 12 mo. 0.60; 1.55***
(1 year post- vs. 1 year pre- implant)
10.0 EQ-5D-5L
1.9±20.8
NYHA ≥ 1 class improvement:
43%
-1132.7*** 100%
7 Thohan 2023 Prospective, single-arm HeartMate II or III LVAD; CardioMEMS implant 101 61.2 75 6 mo. 12.0%; 38.9%*** (non-annualized; based on PAD responder groups) NR 6MWT
56; -6**
mmHg x days NR;
PAP 7-day mean:
Responder 16.5*; Nonresponder 20.3
100%
8 Heywood (US PAS) 2023 Prospective, single-arm NYHA III 710 67.8 57.3 24 mo. 0.37; 0.54; 1.25***
(2 year post- vs.1 year post- vs. 1 year pre- implant)
29 NR mmHg x days NR;
-2.6 mmHg (compared to baseline)
99.6
9 Guichard
(Cordella PROACTIVE-HF)
2024 Prospective, single-arm NYHA III 456 63.5 60.5 6 mo. Composite HFH or ACM: 0.43 Composite HFH or ACM: 0.43 52.8 to 57.8
(p<0.0001)
NR 99.2
Retrospective studies
10 Abraham 2019 Retrospective CardioMEMS implant 1087; 1087 72.7; 72.9 64.9; 64.9 12 mo. 0.65; 0.88*** 22.2; 29.9*** NR NR NR
11 Kishino 2022 Retrospective CardioMEMS implant 1839; 1924 85; 87.3 48.7; 47.5 6 mo. 39.6%; 46.6%**
(HFH readmission rates)
NR NR NR NR
12 Heywood 2017 Retrospective CardioMEMS implant 2000 70 60 6 mo. NR NR NR -434.0*** NR
13 Desai 2017 Retrospective CardioMEMS implant 1114 71.3 63.8 6 mo. 0.37; 0.92***
(rate/patient, 6 mo. post- vs. 6 mo. pre- implant)
12.5 NR NR NR
14 Valika 2023 Retrospective CardioMEMS implant 459 70.8 60.8 12 mo. 0.21; 0.43***
(rate/patient, 6 mo. post- vs. 6 mo. pre- implant).
Pre/Post 30-day admission incidence rate:
0.55***
 Pre/Post 90-day admission incidence rate:
0.45***
12.6 NR NR NR
15 Vaduganathan 2017 Retrospective (MAUDE reports analysis) CardioMEMS implant 5,500 NR NR 3 yr. 155 reports (177 unique AEs); 22 total device-related deaths (0.4%) NR NR NR
16 Assmus (MEMS-HF) 2022 Retrospective CardioMEMS implant 106 68.2 72.6 12 mo. 0.53; 1.54***
(1 year post- vs. 1 year pre- implant)
NR KCCQ
+ 5 points at 12 mo.
Without PH: 54%
IpcPH: 45%
CpcPH: 63%
Without PH: p=0.086
IpcPH: p<0.001
CpcPH p=0.008
NR
17 Desai 2023 Retrospective NYHA II-IV 999 HFH: 67.6 11.6
NP: 71.2
± 9.9
HFH: 60.3
NP: 65.4
12 mo. HFH HR: .73
NP HR:0.75
HFH HR: 1.94
NP HR: 0.63
EQ-5D, 6MHW: non-significant from baseline HFH: -476; -315
NP: -567; -339*
NR

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. 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 2.

Table 2.  Comparison of baseline patient characteristics in the CardioMEMS RCTs

  CHAMPION GUIDE-HF MONITOR-HF
Device (n=270) Control (n=280) Device (n=497) Control (n=503) Device(n=176)

Control (n=172)

Mean Age (years)

61.3 ± 13.0

61.8 ± 12.7

71 (64-76)

70 (64-77)

69 (61-75)

70 (61-75)

Male (%)

72

73

62

63

78.4

72.7

NYHA Class (%)

II

0

0

29

30

0

0

III

100

100

65

65

100

100

IV

0

0

6

5

0

0

LVEF ≥40% (%)

23

20

45

49

27.3

28.5

MPAP (mmHg)

28.9 ± 9.9

29.9 ± 10.0

28 (22-35)

29 (22-35)

24.9 ±10.6

 N/A

Systolic BP (mmHg)

121.2 ± 22.5

123.2 ± 21.0

120 (108-132)

120 (108-132)

112 (103-129)

115 (104-131)

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. Iaconelli (2023) 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 reduction 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.

  • The evidence is inadequate to fully assess which characteristics of the practitioner or facility predict the most successful patient outcomes from use of IPAPS for HF Management.  It was unclear from the evidence if specific treatment conditions are necessary to achieve outcomes similar to those demonstrated in the reviewed clinical studies for all HF patients.  It is possible that less invasive devices or modalities may be as effective in patients with lower risk of HF hospitalization.
  • The evidence is inadequate to fully assess which characteristics of the practitioner or facility predict the most successful patient outcomes from use of IPAPS for HF Management. It was unclear from the evidence if specific treatment conditions are necessary to achieve outcomes similar to those demonstrated in the reviewed clinical studies for all HF patients. It is possible that less invasive devices or modalities may be as effective in patients with lower risk of HF hospitalization.
  • For CardioMEMS, the reviewed evidence suggests that use of IPAPS for HF Management may be a useful therapy for patients with NYHA Class II or III HF to prevent HF hospitalization. The data from a 1- and 2-year Post Approval Study (PAS) and from registry studies appear to support primary HF hospitalization outcomes reported in the RCTs.
  • Furthermore, the short follow-up duration in CardioMEMS randomized trials precludes accurate assessment of benefits in hard clinical outcomes.
  • Large, well conducted studies using an active comparator design (e.g., other PA pressure or atrial devices; novel ambulatory HF monitoring devices) are needed to accurately determine the effect of the IPAPS for HF management on functional, QoL, mortality and morbidity outcomes.
  • Three of the meta-analyses were limited by a lack of access to patient-level data and the heterogeneity of devices reviewed.
  • Study cohorts are predominantly male; therefore, more data is needed for women.
  • Study cohorts have enrolled predominantly White participants, despite evidence of high rates of HF in underrepresented populations. 
  • Future studies should include diversity plans to improve enrollment and retention of participants from underrepresented racial and ethnic populations(e.g., FDA draft guidance Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies Draft Guidance for Industry Opens in a new window 2024).
  • The CardioMEMS RCTs reviewed were not powered to adequately assess mortality outcomes.
  • The length of follow-up of all studies reviewed is relatively short for life-long implanted devices.
  • It is not clear from the data that HF exacerbations (acute worsening of HF symptoms) are reduced with use of IPAPS for HF management, and there is low to very low certainty that use of IPAPS for HF management leads to meaningful improvements in patient symptoms or prognosis.

    For CardioMEMS, data from the COVID-19 period of GUIDE-HF indicate that disease severity and HF hospitalization rates improved similarly in both control and the treatment groups. The reason for the discrepancy between pre-COVID and COVID period data in GUIDE-HF is unclear (Zile 2022).

    Two guidelines are available and summarized in Table 3 below. 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, which provides guidelines on wearables and remote monitoring, including telemonitoring and device monitoring (Heidenreich 2022). The European Society of Cardiology included recommendations for telemonitoring in their 2021 Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure (McDonagh 2021).

    Table 3 includes recent professional society recommendations or consensus statements.

    Table 3. Heart Failure Guidelines Recommendations for Remote Monitoring

    Source COR: Class (Strength) of Recommendation LOE: Level (Quality) of Evidence Recommendation

    AHA/ACC/HFSA

    Heidenreich et al., 2022; p e289

    IIb: Weak; Benefit ≥ Risk B-R (Randomized): Moderate-quality evidence from 1 or more RCTs; Meta-analysis of moderate quality RCTs 1. In selected adult patients with NYHA class III HF and history of a HF hospitalization in the past year or elevated natriuretic peptide levels, on maximally tolerated stable doses of GDMT with optimal device therapy, the usefulness of wireless monitoring of PA pressure by an implanted hemodynamic monitor to reduce the risk of subsequent HF hospitalizations is uncertain (Abraham et al., 2011; Adamson et al., 2014; Givertz et al., 2017; Lindenfeld et al., 2021).
    Value Statement:
    Uncertain Value (B-NR: Nonrandomized)
    Moderate-quality evidence from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies; Meta-analysis of such studies
    2. In patients with NYHA class III HF with a HF hospitalization within the previous year, wireless monitoring of the PA pressure by an implanted hemodynamic monitor provides uncertain value (ACCF/AHA Task Force on Practice Guidelines et al., 2010; Arnett et al., 2014; Halperin et al., 2016; Levine et al., 2019).
     

    European Society of Cardiology

    McDonagh et al., 2021; p 3637

    IIb
    Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure. Usefulness/efficacy is less well established by evidence/opinion.
    B
    Data derived from a single randomized clinical trial or large non-randomized studies.
    Non-invasive HTM may be considered for patients with HF in order to reduce the risk of recurrent CV and HF hospitalizations and CV death (Dierckx et al., 2017)
    IIb
    Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure.
    B
    Data derived from a single randomized clinical trial or large non-randomized studies.
    Monitoring of pulmonary artery pressure using a wireless haemodynamic monitoring system may be considered in symptomatic patients with HF in order to improve clinical outcomes (Abraham et al., 2016).

    Note: Table recreated from: Heidenreich et al., 2022; p e289 (Wearables and Remote Monitoring, Including Telemonitoring and Device Monitoring in 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure); McDonagh et al., 2021; p 3637 (Recommendations for Telemonitoring in the 2021 European Society of Cardiology Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure). CV = cardiovascular; HF = heart failure; HTM= home telemonitoring; LVEF = left ventricular ejection fraction.

    There are no relevant, published appropriate use criteria.

    CMS uses the initial public comments to inform its proposed decision. Public comments that cite the published clinical evidence give CMS useful information. Public comments that contain information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination.

    First Comment Period: April 30, 2024 – May 30, 2024

    During the first 30-day public comment period CMS received 462 comments.  The majority of commenters spoke positively of the use of these devices.  All comments that were submitted during the comment period without personal health information may be viewed by using the following link https://www.cms.gov/medicare-coverage-database/view/ncacal-public-comments.aspx?ncaId=313&fromTracking=Y& Opens in a new window.

    The majority of comments were anecdotes provided by physicians and other health care professionals who utilized CardioMEMS or Cordella among their patients. Three comments were received from medical technology manufacturers, including Abbott, Endotronix, and Pulsli. Three comments were received from professional associations, including the American College of Cardiology and Heart Failure Society of America (joint comment), the American Heart Association and American Stroke Association (joint comment), and Preventive Cardiovascular Nurses Association.

    Second Comment Period: October 30, 2024 – November 29, 2024

    During the second 30-day public comment period CMS received 127 comments.  Similar to the initial public comment period, the majority of commenters spoke positively of the use of these devices and the proposed coverage.  All comments that were submitted during the comment period without personal health information may be viewed by using the following link https://www.cms.gov/medicare-coverage-database/view/ncacal-public-comments.aspx?NCAId=313&ExpandComments=n Opens in a new window

    Additionally, the majority of comments were anecdotes provided by physicians and other health care professionals, many of whom utilized IPAPS for HF management among their patients. We received two comments from medical technology manufacturers, including Abbott and Edwards Lifesciences. We received five comments from professional associations, including American College of Cardiology and Heart Failure Society of America (joint comment), the American Heart Association, the Preventive Cardiovascular Nurses Association, and the Society for Cardiovascular Angiography and Interventions.  One comment was from a patient advocacy organization, The Mended Hearts, Inc. One comment was  from an industry organization, the Advanced Medical Technology Association (AdvaMed).  One comment was from a health research advocacy organization, the National Center for Health Research.

    Comment:  The majority of commenters stated support for the use of IPAPS for HF management.  Some of these commenters emphasized that they would expect the device to greatly reduce HF hospitalizations.  Some also mentioned that fewer hospitalizations could result in reduced healthcare expenditures for HF patients.

    Response:  CMS appreciates these thoughtful comments.  We agree that one of the goals of IPAPS for HF management is a reduction in HF hospitalizations, and this is incorporated into our criteria for primary outcomes of CED studies. 

    Comment:  Many commenters believed that IPAPS could lead to better HF symptom management, increased patient satisfaction, and improved quality of care overall.  Some clinicians reported that patients felt more involved with their HF care and that their care team was watching out for them.  They also believe that the device could help guide diuretics when fluid status would otherwise be unknown or unclear.  Some commenters thought this device could be helpful for those with limited treatment options.  Some commenters thought it could be particularly beneficial for patients who live a far distance from their healthcare facility by reducing the number of in-person visits or have limited transportation, and thus possibly improving health equity.

    Response:  We thank commenters for their support.  We always appreciate clinicians, patients, and advocates sharing their experiences, and we have taken all their feedback and guidance into account when writing the language for the final NCD.

    Comment:  The majority of commenters expressed general support for Medicare coverage of IPAPS for HF management.  They shared positive anecdotes about patients who had received this device. Some commenters believed that the largest barrier to using this device was insurance denials, and others noted that they thought the costs associated with this device would be much less than the potential costs of the HF hospitalizations and readmissions that this device could prevent.

    Response:  We thank commenters for their support and their thoughtful comments.

    Comment:  Several commenters did not support a positive coverage decision for IPAPS for HF management for various reasons.  Some believed there was a lack of evidence regarding the efficacy of the device. For example, they observed that GUIDE-HF found no statistically significant difference in a composite measure of mortality, HF hospitalizations, and urgent HF hospital visits between the control and the device group in the overall study; indicated that CHAMPION was flawed due to differences in patient contact resulting from reported protocol deviations; and asserted that the MONITOR-HF trial in the Netherlands was subject to bias.  Another commenter was concerned that MONITOR-HF did not show reduction in non-HF hospitalizations. Some commenters raised concerns that that the average ages and race/ethnicity of study participants were not generalizable to Medicare beneficiaries.  They also thought there were other treatment approaches available to manage HF and expressed concern for the possible risks associated with this device, such as infection.

    Response:  We recognize the concerns that commenters have raised and have taken them into consideration as we finalized this decision.  There is a risk of infection when patients undergo any procedure, including implantation of a PAPS; however, IPAPS trials demonstrate relatively low infection rates.  We have extensively examined the evidence from the key clinical trials, including CHAMPION-HF, GUIDE-HF, and MONITOR-HF, and summarize our conclusions in IV. B. CMS Analysis for Coverage of IPAPS for HF Management.  We have acknowledged the limitations noted by these commenters, and it is because of these evidence gaps that we believe more research is needed, particularly for the subgroups we identify.

    However, we believe the evidence overall, while insufficient, is promising, and note that the latest trial (MONITOR-HF) was not impacted by COVID and achieved its pre-specified outcomes (for both quality of life and HF hospitalizations).  The limitations of being a small trial conducted wholly within the Netherlands prevents us from confidently concluding that its results are generalizable to the US Medicare population in its typical, real-world care settings.  Thus, CMS maintains that CED is the most appropriate policy option to fill these evidence gaps for IPAPS.

    Comment:  One manufacturer expressed support for the proposed NCD criteria regarding furnishing IPAPS for HF management according to the FDA market-authorized indication.

    Response:  We appreciate this comment. We have finalized as proposed.

    Comment:  One IPAPS manufacturer expressed support for the NCD patient criteria as proposed.

    Response:  We appreciate this comment.

    a)                  Patient Diagnosis

    Comment:  One commenter asked CMS to consider including NYHA Class IV patients due to limited treatment options for these patients.

    Response:  The proposed patient criteria: “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)” reflects the current FDA indications for IPAPS for HF management systems, which are for NYHA Class II and Class III patients.  The criteria are also consistent with the trial evidence reviewed for this NCA.  We have finalized as proposed.

    b)                  On GDMT for 3 months prior to PAPS implantation

    Comment: Some commenters supported CMS’ proposed requirement that patients be “[o]n maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months prior to PAPS implantation.” 

    Response: We appreciate these comments.

    Comment:  Some commenters recommended that CMS either completely remove or reduce the number of months that patients must be on maximally-tolerated GDMT prior to PAPS implantation.  Commenters noted that it can take some patients more than 3 months to achieve maximally-tolerated GDMT, and that patients who had struggled to reach maximally tolerated GDMT before implantation are able to do so afterwards.

    Response:  Having a patient optimized to the extent possible on standard-of-care treatments including GDMT prior to PAPS implantation is consistent with trial criteria, guidelines, and expert reviewer recommendations.

    For newly diagnosed HF patients, physicians start medications sequentially, not all at once.  Initial drugs may impact renal function or blood pressure, informing changes in their dose, and/or which drug to add next.  If GDMT drugs were all started at once, and there was a side effect or adverse event, it would be hard to know which drug/dose was the culprit.  The appropriate, gradual build up to maximally-tolerated GDMT takes about 3 months at minimum (consistent with clinical expert reviewer advice), and patient adherence – a key factor for success of IPAPS for HF management – can also be demonstrated during this period.  Patients must demonstrate not only adherence, but also that they respond to some combination of GDMT drugs, or else IPAPS, which merely guides the use of such drugs, will not help them.

    We proposed the language, “[o]n maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months prior to PAPS implantation.”  We clarify that this is a total of 3 months on GDMT, including the ramp up; also, a HF hospitalization that occurs during this period does not “restart the clock.”  We thus are modifying our final decision language to reflect this allowance for ramp up, and to avoid misinterpretation that the patient must reach stable doses of GDMT with stable clinical results, prior to receiving an IPAPS.  The revised language states that patients must be, “[o]n guideline-directed medical therapy (GDMT) for at least 3 months with the goal of achieving optimal or maximally-tolerated GDMT prior to PAPS implantation” (emphasis added).  As one expert reviewer opined, it is those patients who never achieve stability who might benefit most from continuous IPAPS monitoring, while patients who readily achieve and maintain such stability with standard-of-care treatment are unlikely to benefit further from IPAPS.

    This latter insight leads to our final point: time is needed to ramp up medications and assess not just negative patient responses but also positive ones.  Standard-of-care administration of GDMT, and CRT (with or without an ICD component) if needed, along with other evidence-based interventions, can by themselves improve patient hemodynamics, NYHA classification, and LVEF.  Patients need to be given a chance to stabilize and improve using the existing standard of care before jumping to the next step with a device that is implanted for life and carries potential risks.

    c)                  ICD, CRT-P, CRT-D Implantations

    Comment:  A few commenters disagreed with CMS’ proposed policy that ICD and/or CRT implantation, if appropriate for the patient, must occur at least 3 months prior to PAPS implantation.  Specifically, one commentor stated: “The societies would like to make note that while CRT devices are expected to aid in HF management, ICD devices are not anticipated to improve symptoms or signs of HF.  Therefore, we believe that requiring ICD implantation more than three months prior may be unnecessarily restrictive.  We recommend that ICD be removed from this requirement.”

    Response:  We appreciate the comments on this topic and are providing a fuller explanation.  We proposed the language, “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.”  We are aware that ICDs (unlike CRTs) prevent sudden cardiac death and are not intended to improve signs or symptoms of HF.  The requirement to not implant an IPAPS until 3 months after implantation of a CRT and/or ICD (if needed), while matching the 3-month period to achieve optimal or maximally-tolerated GDMT along with other standard-of-care treatments, was also intended “to avoid manipulation of the lead” per the exclusion criteria from the MONITOR-HF trial supplement.  Thus, any device (CRT-P, CRT-D, ICD) that has leads would require a 3-month wait for this reason alone.

    d)                 Reliable connectivity for IPAPS data

    Comment:  One commenter recommended replacing the word “possessing” (as appeared in the proposed decision language) with “having access to” in order to avoid creating an unnecessary barrier for certain patients.

    Response:  We appreciate this comment, and indeed the CMS Coverage Analysis section of our proposed decision gave the rationale that “[p]atients must have access to reliable connectivity (e.g., wireless connectivity in the case of CardioMEMS) for the IPAPS system to work.” We proposed the language, “Possessing adequate technology to ensure reliable remote connectivity to the IPAPS device.”  To remove confusion, we have revised our final decision language to reflect that patients do not have to have personal possession of the connectivity equipment or services; rather, they must have daily access to these, as use of an IPAPS for HF management requires patients to collect and submit data daily.  As an example, HF patients in an assisted-living facility may have daily access to adequate connectivity, but do not own or possess it themselves.  Thus, the revised language states, “[h]ave access to reliable connectivity to ensure daily collection and submission of IPAPS data.”

    e)                  No implantation during a hospital admission for an acute HF episode

    Comment:  Some commenters supported the proposed requirement that patients, “Must not have PAPS implantation occur during a hospital admission for an acute HF episode.”

    Response:  We appreciate these supportive comments, and we are finalizing as proposed.

    Comment:  Some commenters believed that PAPS implantation should be allowed to occur during a patient’s hospitalization for an acute HF episode (with one commenter suggesting implantation during a patient’s second HF hospitalization).  Some cited that implanting during a patient stay would increase access to care, especially for patients living in rural areas or those with limited transportation.  One manufacturer noted that patients were not excluded from the CardioMEMS GUIDE-HF clinical trial if they met all other inclusion/exclusion criteria but were hospitalized at the time of study enrollment.

    Response:  Thank you for these comments.  After much deliberation, we are finalizing our proposed criterion that patients “[m]ust not have PAPS implantation occur during a hospital admission for an acute HF episode” for multiple reasons.  First, the Instructions for Use/User’s Manual for both CardioMEMS (the device in this IPAPS class for which the most trial data exists) and Cordella (which is undergoing FDA trials), requires a right heart catheterization be performed to calibrate the device.  The goal of the right heart catheterization is to calibrate the IPAPS, documenting PA pressures when the patient’s volume status is stable, and that is unlikely to happen during an inpatient stay for an acute HF episode.

    Second, inpatients are receiving care that may include diuresis, medication adjustments, labs, chest x-rays, echocardiography, and, in special circumstances, use of a temporary pulmonary arterial catheter (e.g., Swan-Ganz).  An IPAPS does not have evidence in this setting.

    Third, the IPAPS itself will not benefit the patient at home absent a HF expert-led clinical team, with a plan, effective communications, and medication adherence already established.  Ensuring this is established prior to implantation is critical to success and is consistent with trial protocols and expert reviewers’ recommendations.  And note that in trials, the existence of this HF team was automatically assured per trial protocols; one cannot make that assumption for any patient hospitalized for HF in general community practice.

    Fourth, elective procedures are rarely, if ever, performed in unstable patients.  If patients hospitalized for acute HF are not stable, they would not be discharged and would continue to receive higher-level inpatient care.  If they are stable, they can follow up as an outpatient.  If an IPAPS were to be placed in hospital, out of convenience or for other reasons, it would have to be calibrated by right heart catheterization out of hospital anyway (as discussed above), in which case the implantation could occur at that same time.  Note that this holds true regardless of where the patient lives, and whether this was the patient’s first or second hospitalization.  This NCD is silent on the exact timing after hospital discharge of when a patient who qualifies for IPAPS for HF management may receive one.

    We continue to believe that an IPAPS must be ordered by the cardiologist who is taking long-term responsibility for the patient’s monitoring and care (in accordance with CMS-approved CED study protocols), and this is reflected in the criteria for referring physicians in this policy.  An inpatient team or hospitalist who notices recurrent hospitalizations does not, alone, meet the CED criteria; however, they can be an important link to keep the patient’s established care team informed.

    Comment:  One IPAPS manufacturer expressed support for the NCD physician criteria as proposed.

    Response:  We appreciate this comment.

    a)                  Referring Physician

    Comment:  Some commenters mentioned that requiring experience in advanced HF management (the wording originally proposed) exceeds what would be needed to manage patients with IPAPS.  Other commenters requested that CMS define “experience in advanced HF management” or suggested that the word “advanced” be removed from the description.

    Response:  We appreciate these comments and are modifying our final decision language based on them.  We proposed the language, “[p]hysicians referring the above Medicare beneficiaries and managing them post implantation must be cardiologists with experience in advanced HF management.”  We noted in the proposed memo that cardiologists referring patients and managing them post implantation do not have to be board certified HF specialists.  This is due to the dearth of numbers and geographic distribution of such specialists.  We are now clarifying that cardiologists need to have training and experience in HF management, not in advanced HF management, which could be misinterpreted as implying a need for experience specifically with severe, advanced cases, such as patients awaiting heart transplant.  To be eligible for IPAPS, patients must be NYHA Class II or III; however, as the device is implanted for life, we anticipate continued use of it once a patient progresses to Class IV.  Note that further detail as to what constitutes sufficient training and experience in HF management for cardiologists would be proposed and justified by clinical investigators in CED study protocols submitted for CMS approval.  Thus, we are finalizing the revised language, “[p]hysicians referring Medicare patients and managing them post implantation must be cardiologists with training and experience in HF management.”

    Comment:  Some commenters suggested that Nonphysician Providers (NPPs) or Advanced Practice Providers (APPs) should be able to refer patients for this device, not just cardiologists.

    Response:  We appreciate these comments and recognize the important contributions of NPPs and APPs to integrated cardiology practices.  However, we believe that the extensive training and expertise of a cardiologist is a key part of comprehensive, longitudinal care for HF patients, and note that the promising evidence seen in trials was produced primarily by cardiologist-led care teams.

    b)                 Implanting physician

    Comment:  One commenter requested that CMS clarify what was intended by “pulmonary arterial catheterization and intervention.”

    Response:  We appreciate this comment.  We proposed the language, “[p]hysicians implanting the device must have advanced training and experience in pulmonary arterial catheterization and intervention.”  Experience in pulmonary arterial catheterization and intervention is important for this procedure to be successful.  Clinical investigators designing study protocols for CED studies may propose and justify training and proctoring requirements that would allow physicians with experience in similar procedures to meet the requirement for training and experience in pulmonary arterial catheterization and intervention. In this light, we strike the word “advanced” as it is unnecessary and may cause confusion.

    Comment:  One commenter suggested that CMS should specify that implanting physicians have training in hemodynamics.

    Response: We believe the implanting physician criteria, as finalized (see above), would include this type of knowledge broadly.

    a)                  Support for CED for IPAPS for HF Management

    Comment:  One IPAPS manufacturer expressed support for the CED study criteria as proposed because they thought the criteria outlined the need for rigorous study designs that address the evidence gaps.

    Response:  We appreciate this comment.

    b)                 Concerns about CED

    Comment:  One commenter believed that CED is not the right coverage mechanism for IPAPS for HF management.  This commenter thought the clinical trials, specifically CHAMPION, GUIDE-HF, and PROACTIVE-HF, provide strong evidence of efficacy, and they thought CED could restrict access to the technology, create administrative burdens, deter participation, and delay benefits.  The commenter believed combining coverage with ongoing data collection would better balance evidence needs with patient care.

    Response:  The purpose of this CED policy is exactly to combine coverage – for all patients who qualify, not just a select few – with ongoing data collection aimed at filling well-known evidence gaps that were discussed extensively in this NCA.  With a registry as the CED backbone, and multiple studies being pursued in parallel, there is no restriction on the number of patients who may participate, providing they meet criteria.  These criteria in turn are based primarily on the major inclusion and exclusion criteria of key trials.  We believe these trials and other supporting studies demonstrate that the evidence base has significant gaps but is promising enough to allow CED.

    We strive to strike an appropriate balance between reducing burden on providers and obtaining necessary data to inform future coverage determinations.  We encourage investigators to develop rigorous evidence development strategies that make use of real-world data, and we continue to evaluate studies using real world evidence when making coverage determinations.  We will evaluate published, peer-reviewed evidence periodically, following the effective date of this coverage decision, and reconsider the policy when appropriate.

    a)                  Primary outcomes

    Comment:  One commenter asked CMS to direct study sponsors to collect heart failure-related hospitalizations for a 24-month period post-implant rather than for 12 months.

    Response:  We appreciate this comment.  The proposed language requires, “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.”  Thus, we require collection of all data for the primary outcome (including HF hospitalizations) for a minimum of 24 months, not 12 months.  We did not propose a shorter time frame for either primary or secondary outcomes.  As typically done in studies, we anticipate that CED study protocols will have provisions for following patients past the 24-month period specified as the minimum needed for the primary analysis.  Based on prior trials, we anticipate that CED studies will aim to demonstrate a substantial reduction of HF hospitalizations (if not mortality).  We are finalizing as proposed.    

    b)                  Active comparator

    Comment:  One commenter asked CMS to further clarify what was meant by an “active comparator.”  The commenter quoted our analysis which stated that an active comparator is “inherent in RCTs that prospectively compare randomized intervention and control groups, but may be seen in other study designs, such as those employing propensity-score matching or instrumental variables.”  The commenter recommended that CMS state that study designs may use propensity-score matching or instrumental variables for active comparators.

    Response:  We appreciate this comment.  We proposed the language that CMS-approved CED study protocols must include an active comparator. We offer this clarification: “[t]he active-comparator arm refers to the group of participants in a clinical trial who receive a treatment that is considered effective and most often currently used in clinical care.  Outcomes from the active-comparator arm are compared to the experimental arm to determine if the therapy or intervention being studied works better or is safer than the current treatment.”[1] The active comparator design potentially helps to reduce both measured and unmeasured confounding.  A study design without an active comparator will typically not be considered fit-for-purpose by CMS, except in unusual circumstances where the conditions for single-arm study credibility are met and the construction of a control group is not feasible.  In observational study designs, randomization is not used, but various methods (e.g., propensity matching, use of instrumental variables) may be employed to simulate randomization and construct an active comparator that minimizes the potential for bias/confounding.  We are finalizing as proposed.

    c)                  Care management plan

    Comment:  One commenter specifically supported CMS’ decision to include requirements for a multidisciplinary HF team involved with the patient’s care management plan.

    Response:  We appreciate this comment.

    Comment:  One commenter suggested that follow up care for IPAPS such as remote monitoring and medication adjustments should be included as part of the NCD coverage criteria.

    Response:  We appreciate this comment.  We proposed the language that CMS-approved CED study protocols must include, “[a] care management plan that: [i]dentifies 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.”  We note that this criterion includes a care management plan with follow-up patient monitoring and medication management.  We are finalizing as proposed.

    Comment:  A few commenters believed that patient adherence and a reliable and well-staffed IPAPS monitoring team could positively impact health outcomes.  They explained that monitoring the data produced daily by the device could increase burden on the care team, and so they believed the device should only be implanted if a strong monitoring team and plan is in place.

    Response:  CMS thanks these commenters for their recommendations.  We share this concern that patient adherence and a well-staffed and trained monitoring team are key for the success of IPAPS for HF management.  This is exactly the rationale for the criteria we specify above.  We are finalizing as proposed.

    d)                 Subgroup analysis

    Comment:  A couple of commenters mentioned CMS should direct study sponsors to ensure equal representation of women, patients from underrepresented ethnic and racial groups, and older patients to address disparities and reflect the diversity of heart failure patients.

    Response:  We appreciate these comments.  The proposed CED study criteria included subgroup analysis by age (75+ years), sex, and race and ethnicity (among other subgroups).  The priority for more balanced representation in studies is further reinforced in the section on CED Study Criteria (III.3.f.(7) and (8)) of this decision, which describe the Study Population and Subgroup Analyses.  As such, we anticipate that investigators submitting CED study protocols for CMS approval will include robust plans for recruitment and retention of marginalized populations, consistent with these criteria.  We are finalizing as proposed.

    Comment:  A couple of commenters expressed concern with the proposed language that “all other uses of IPAPS are non-covered” could inadvertently prevent coverage for IPAPS under Investigational Device Exemption (IDE) studies for other indications.

    Response:  We appreciate these comments.  To address this concern, we are revising the language to clarify that “IPAPS for HF management is not covered for patients outside of a CMS-approved study. Nothing in this NCD would preclude coverage of IPAPS for HF management through NCD 310.1 (Clinical Trial Policy) or through the Investigational Device Exemption (IDE) Policy.”

    Comment:  A few commenters pointed out that, in their experience, IPAPS for HF management may increase equitable access to care, especially for beneficiaries in rural areas, and reduce clinical bias through objective feedback provided by the sensor.

    Response:  We appreciate these thoughtful comments and thank commenters for their support.

    Comment:  Some commenters believed a ‘negative’ coverage decision could limit some of the efforts working toward equitable access.  They also expressed concerns that the device could be inaccessible to beneficiaries without reliable internet access, and recommended that CMS take steps to ensure appropriate inclusion of underrepresented populations in CED studies. 

    Response:  CMS appreciates these concerns.  This CED provides coverage without restriction on the number of patients who may be covered for IPAPS, as long as they meet criteria.  These criteria, including access to reliable connectivity, are necessary for successful use of IPAPS for HF management, as supported by key trials.  As discussed in a previous comment/response, better inclusion of underrepresented populations, and subgroup analysis of them, is a priority for all CED studies. 

    Comment:  Several commenters mentioned topics such as payment rates, or recommended use of IPAPS for conditions outside of the FDA-approved label, or for diseases or conditions not specifically addressed within CMS’ evidence review or identifiable with subgroup analysis.

    Response:  These comments are outside of the scope of this NCD.

    Comment:  One commenter observed that a study had been incorrectly categorized as excluded from our analysis.

    Response:  We appreciate this comment and added the study to the Bibliography.

    While the overall lifetime risk of HF is similar between genders, women are less likely to receive non-pharmacological therapies (Mwansa 2021). Evidence indicates that women respond differently than men to pharmaceutical and device-based management of HF. Yet, women are underrepresented in clinical trials for HFrEF drug and device therapies that form the basis of evidence-based HF management recommendations (Lam 2019). Relative to the prevalence of HFrEF, women were also substantially underrepresented in the studies described in this review.

    Disparities across key indicators of the US population burden of HF (including incidence, prevalence, and outcomes) have been identified among women, Hispanic, and Black individuals (Bozkurt 2023, Butler 2019). There is very little data on the epidemiology of HF in Hispanic, Latinx, American Indian, Alaska Native, and South Asian populations (Bozkurt 2023, Roger 2021). Black and Hispanic populations have a higher prevalence of HF than White populations, and Black women have the highest prevalence of all racial and ethnic groups (Tsao 2022). HFpEF is the most prevalent HF phenotype for White women, while HFrEF predominates among Black women (Mwansa 2021). Black patients not only have a higher incidence of HF than other racial groups, but they also have higher admissions for HFrEF and worse overall survival (Lewsey 2021, Miller 2021). Despite these statistics, these groups were underrepresented in the reviewed RCTs related to efficacy and safety of the CardioMEMS HF System. For the CHAMPION and GUIDE-HF randomized trials, White patients accounted for ≥73% of total enrolled participants. The MONITOR-HF randomized trial authors did not report race/ethnicity data, but the trial was conducted entirely in the Netherlands. The PROACTIVE-HF single-arm study reported race in baseline demographics but no subgroup analyses. CMS is interested in broader evidence on understanding whether there are differences in outcomes with the use of IPAPS in HF among patient subgroups as differences in outcomes among different subgroups may indicate other un-measured differences in care that could affect outcomes. There is a particular paucity of evidence assessing the impact of race on health outcomes for patients using IPAPS in HF management. This evidence could help assess whether unintended barriers might impair access to IPAPS for non-white Medicare patients.

    IV.          CMS Coverage Analysis

    National coverage determinations (NCDs) are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally by Medicare (§ 1869(f)(1)(B) of the Social Security Act (the Act)). In general, in order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B and must not be otherwise excluded from coverage. Moreover, with limited exceptions, items or services must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§ 1862(a)(1)(A) of the Act).

    When the available evidence is insufficient to demonstrate that the items and services are reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member under section 1862(a)(1)(A) of the Act, coverage with evidence development (CED) has been used to support evidence development for certain items and services that are likely to show benefit for the Medicare population. [2]  CED has been a pathway whereby, after a CMS and AHRQ review, Medicare covers items and services on the condition that they are furnished in the context of clinical studies or with the collection of additional clinical data.[3] (See CMS’ CED Guidance Document Opens in a new window.)  CED relies primarily on the statutory exception in section 1862(a)(1)(E) of the Act, which effectively permits Medicare payment for items and services that are reasonable and necessary to carry out research conducted pursuant to section 1142 of the Act.

    Section 1142 of the Act describes the authority of AHRQ to conduct and support research that appropriately reflect the needs and priorities of the Medicare program.[4]

    This section includes CMS’ analysis of the evidence related to IPAPS for HF Management. Relevant details from studies listed in Table 1: Key Studies for IPAPS for Heart Failure Management above are provided in context when key study findings or limitations are discussed with respect to coverage.

    The evidence in Sections III.D-E indicates that there is some benefit for some HF patients with IPAPS in defined clinical study conditions. However, as identified in Section III.F. Limitations of Evidence, there are crucial limitations to the evidence base for IPAPS for HF management and questions relating to appropriateness for Medicare patients and the clinical utility of IPAPS HF management that need to be answered before CMS would be able to determine if coverage is reasonable and necessary under § 1861(a)(1)(A) of the Act.

    As further discussed below in the analysis, we are using CED for IPAPS for HF Management. In Section IV.B.1-3 below, we analyze key findings and shortcoming of the evidence, and in Section IV.B.4 below, we describe how those elements translate into the evidence-based rationale for each of the CED study parameters (e.g., patient, physician, study criteria) that aim to fill the evidence gaps.

    The overall objective for the critical appraisal of the evidence is to determine to what degree we are confident that the specific assessment questions raised in a National Coverage Analysis (NCA) can be answered conclusively. When conducting NCAs for an item or service under the reasonable and necessary statute, CMS generally makes three kinds of assessments: (1) The quality of relevant individual studies; (2) What conclusions can be drawn from the body of the evidence on the direction and magnitude of the intervention’s potential harms and benefits; and (3) The generalizability of findings from relevant studies to the Medicare beneficiary population.

    (See CMS’ Evidence Review Guidance Document Opens in a new window.)

    CMS coverage determinations for diagnostic tests (to include, for example, interpretations of imaging or data accumulated from external devices or implanted devices such as IPAPS) consider whether results of the test guide clinical management (see 42 CFR 410.32(a)) that lead to meaningful improvement of health outcomes for Medicare beneficiaries, as demonstrated in peer-reviewed publications of clinical studies. It is through this construct that we assess the totality of evidence for FDA market-authorized IPAPS with remote monitoring for HF management of Medicare beneficiaries.

    Changes in clinical management informed by test results are meaningful if they lead to improved patient health outcomes.  The relevant outcome may depend on the disease, as well as the patient’s clinical scenario, pathophysiology, and preferences.  Patient-centered primary outcomes for trials of HF diagnostics and treatments have included mortality, HF hospitalizations, a composite of these, and quality of life.  These patient health outcomes are central for determining whether a diagnostic test for HF is reasonable and necessary under the Act.  CMS’ approach for assessing evidence for diagnostic tests is summarized in the Federal Register:

    Specifically for diagnostic imaging tests, the overall assessment focuses on whether use of the test to guide patient management and treatment improves health outcomes (also referred to as clinical utility). Before appropriately reaching a consideration of outcomes, two fundamental properties of diagnostic tests need to be established: (1) the test accurately and reliably measures the intended analyte, factor, or component (also referred to as analytic validity); and (2) the test accurately and reliably identifies the condition or disorder of interest (also referred to as clinical validity).  [83 Fed. Reg. 15573 (April 11, 2018)]

    As a change in hemodynamics (blood flow through vessels) precedes clinical manifestations of HF, the purpose of IPAPS is early detection of that change, allowing medical intervention to prevent symptom onset or, this failing, further exacerbation and subsequent hospitalization. A care team led by a HF specialist would use the patient’s daily PA pressure trends and other clinical data as inputs to remotely apply evidence-based medication protocols to “guide subsequent decisions on starting, stopping or modifying treatment” to improve “subsequent health outcomes” (Mol 2003).

    The peer-reviewed medical literature has demonstrated that consistent use of GDMT, which the IPAPS is intended to guide, produces meaningful health benefits for HF patients (Heidenreich 2022). GDMT has been most effective for HF patients with reduced ejection fraction (HFrEF); however, a new class of HF drugs, SGLT2 inhibitors, appears to be effective for HF patients with preserved ejection fraction (HFpEF) as well (Jaiswal 2023, Solomon 2022, Anker 2021).

    a)                 Randomized Controlled Trials

    The evidence presented in Section III. E. identified three key, contemporary randomized controlled trials (RCTs) and numerous other studies evaluating the impact of an IPAPS device (CardioMEMS) on HF patient outcomes.

    The CHAMPION trial demonstrated that use of CardioMEMS reduced HF hospital admissions by 28% at 6 months, and 33% at 18 months, compared to a control group receiving standard of care alone. In the open access phase (a total of 13 months), when IPAPS data became available for all patients, rates of HF hospital admissions in the former control group were reduced by 48% compared with rates of admissions in that control group during the randomized phase (Abraham 2011, 2016; Givertz 2017). These between-group comparisons (“effect sizes”) were widely regarded as clinically meaningful; however, there were significant limitations to the trial as it was non-blinded, and the care team for the IPAPS-monitored group provided substantially greater patient contact and guidance, potentially accounting for the improved outcomes in that group.

    The GUIDE-HF trial was designed to correct perceived flaws (most importantly the imbalanced patient contact) in the CHAMPION trial with protocols specifying the amount of, and scripted guidance for, care team contact with patients in each group. The aim of GUIDE-HF was “to evaluate whether haemodynamic-guided management using remote pulmonary artery pressure monitoring could reduce heart failure events and mortality in patients with heart failure across the spectrum of symptom severity (NYHA functional class II–IV), including those with elevated natriuretic peptides [i.e., proteins that regulate blood circulation and pressure] but without a recent heart failure hospitalization” (Lindenfeld 2021). Overall trial findings found no difference between the intervention and control groups for a composite endpoint of mortality and total heart failure events (including hospitalizations) (Lindenfeld 2021).

    A widely acknowledged confounder is that GUIDE-HF was launched during COVID-19, with its attendant changes in patient care dynamics. However, a prespecified, secondary analysis of the pre-COVID-19 data found a lower rate of the composite outcome in the intervention group, driven by a lower HF hospitalization rate. While this subgroup analysis was not powered for definitive results, and thus remains hypothesis-generating only, it supports the case that use of IPAPS monitoring may improve health outcomes by reducing hospitalizations for HF patients (Lindenfeld 2019, 2021).

    A separate, prespecified secondary analysis of the pre-COVID-19 data assessed whether outcomes depend on the patient’s LVEF (with guideline-defined subgroups of ≤40%, 41%-49%, and ≥50%) rather than symptom severity (Zile 2022). The authors concluded unequivocally that “hemodynamically-guided management of patients with HF based on direct measurement of filling pressures is effective across the EF spectrum in reducing the HF hospitalization endpoint in an expanded patient population of NYHA functional class II-IV HF enrolled with a previous HF hospitalization or increased natriuretic peptides” (Zile 2022). However, GUIDE-HF was not powered for definitive subgroup analysis, to include for EF. Consequently, the graphs and forest plots appearing just above this quoted text reveal a less than unequivocal picture. For example, the high variability of results for the HFmrEF subgroup reflected in the broad confidence intervals in the forest plots may result from the small number of trial participants in this subgroup. This means there is insufficient data to reach definitive conclusions. If a trial is not powered for a given subgroup analysis, the standard practice is to test for “interactions” or “effect modification” (mathematically the same, these are applied and interpreted differently). However, such methods are widely considered hypothesis-generating only, a conclusion echoed in contemporary CMS NCDs (e.g., for ICDs, with respect to the CRT subpopulation in the DANISH trial; CMS 2016). Zile and coauthors assert that health outcomes do not depend on EF because, “For each endpoint, the treatment by EF interaction was not statistically significant for either the primary endpoint (P = 0.71) or HF hospitalizations (P = 0.95)” (Zile 2022). But this could be explained either by no true difference between the EF subgroups (in which case the authors are right, and they could well be), or alternatively by the small numbers informing the subgroup analysis.

    We conclude based on this secondary analysis (and others) that the evidence for improved health outcomes (clinical utility) across the EF spectrum is hypothesis-generating, not definitive, and so this remains an important evidence gap for CED studies to address. We reach a similar conclusion for patient selection based on elevated natriuretic peptides (e.g., NT-proBNP) alone, who have not had a recent HF hospitalization. The manufacturer has a preliminary design for a study that would address the question of whether outcomes are affected by patient selection based on HF hospitalizations vs laboratory parameters alone.

    In the MONITOR-HF trial, the third and most recent of these contemporary RCTs, patient selection included recent HF hospitalization, regardless of EF; use of natriuretic peptides was exploratory only (Brugts 2023).  MONITOR-HF found that IPAPS monitoring with CardioMEMS and highly protocolized[5] remote medication management reduced HF hospitalizations by 44% compared to a standard-of-care control group (with no change in non-HF hospitalizations between the randomized groups).  The IPAPS-monitored group also experienced improved quality of life (as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (Brugts 2023).

    The MONITOR-HF authors believe their findings echo those of CHAMPION but without its perceived flaws: “Our results are consistent with the findings of the CHAMPION trial. However, because CHAMPION recruited patients well over a decade ago, we saw a much higher level of GDMT and contemporary standard care in our study. Essentially, the MONITOR-HF trial showed one of the highest uptakes of ARNIs and SGLT2-inhibitors in trials to date, and the use of mineralocorticoid receptor antagonists was also much higher in this trial than in most other trials. The added value of remote monitoring in our study cannot therefore be ascribed to relatively lower levels of GDMT in standard care patients, a potential reason that was discussed after the CHAMPION findings” (Brugts 2023).

    However, MONITOR-HF was small (N = 348) and lacked power both for the endpoint of mortality and for subgroup analyses (across the EF spectrum, and of racially and ethnically diverse populations, women, etc.). Finally, MONITOR-HF reflects neither Medicare beneficiaries nor their usual care settings as the trial was conducted entirely in the Netherlands. We do consider well-designed studies from high-quality health systems conducted abroad, but other aspects, such as small size and the high patient adherence to protocols (compared to typical US studies), limit the conclusiveness and generalizability of this one trial.

    As a final note on RCTs, the strongest assessment of whether an IPAPS system provides independent and meaningful benefit for HF patients would be a head-to-head RCT comparing intense remote monitoring and medication changes by a care team (which is beyond the standard of care), with and without an IPAPS monitoring device. To our knowledge no RCT with this design has been completed to date.

    b)                  Meta-analyses

    While the above RCTs represent the primary evidence, meta-analyses of combined data from multiple trials provide additional insights, especially for certain subgroups. A recent meta-analysis by Curtain evaluated whether beneficial health outcomes depend on a patient’s baseline LVEF, and concluded that “[IPAPS]-guided treatment was effective at reducing worsening heart failure (HF) events in patients with an EF of <50%; it is uncertain if patients with HF with preserved EF receive the same benefit” (Curtain 2023). Other meta-analyses have concluded that trials of IPAPS monitoring devices have demonstrated a significant reduction in HF hospitalizations but no impact on mortality (Urban 2024, Iaconelli 2023, Clephas 2023). No RCT or meta-analysis to date has shed definitive light on these important subgroups: NYHA Class II versus III, EF status, ICD and/or CRT status, women, minorities, etc.

    The most recent meta-analysis to date (Urban 2024)[6] provides the following insights relevant to this CED NCD:

    (a) IPAPS should be used to guide GDMT itself (which might not have been effectively “stabilized” despite a 90-day attempt prior to IPAPS) and not just diuretic use;

    (b) past trials may not have shown a mortality benefit for HF patients with reduced ejection fraction (HFrEF) because that data set included patients with preserved LVEF (HFpEF) who were more prone to death due to non-cardiac causes, which raises the prospect that future studies could show a mortality benefit specifically for HFrEF patients; and

    (c) SGLT-2 inhibitors could provide benefit (in terms of reduced HF hospitalizations if not mortality) to the subgroup of HFpEF patients, a group that has been notoriously difficult to treat with any HF drugs or devices (Anker 2021, Solomon 2022, Jaiswal 2023).

    The evidence supporting use of IPAPS for this HFpEF subgroup is still emerging. As the New England Journal of Medicine (NEJM)-invited editorial on the DELIVER trial states, “Owing to the very low enrollment of patients who identified as Black individuals in both the DELIVER trial and the EMPEROR-Preserved trial, it is still not known whether this patient subgroup benefits from treatment with SGLT2 inhibitors. It is also unknown whether the benefits of SGLT2 inhibitors extend to patients with heart failure and a preserved ejection fraction due to cardiomyopathies (e.g., hypertrophic cardiomyopathy and restrictive cardiomyopathies due to amyloidosis, sarcoidosis, or other causes), since patients with these cardiomyopathies were excluded from both trials” (Margulies 2022). Thus, more data is needed on subgroups within the HFpEF population.

    A recently-published study (PROACTIVE-HF) for Cordella was the basis for FDA premarket approval of Cordella for NYHA Class III HF patients who are at home on diuretics and GDMT. FDA is requiring a post-approval study (PAS) “to collect additional evidence of continued safety and effectiveness in the NYHA Class III patient population as well as to address the uncertainty FDA noted in the enrolled patient population in the PROACTIVE-HF study” (FDA 2024“a”).

    We considered the strengths and limitations of key contemporary trials, secondary- and meta-analyses of their data, follow-up and other longitudinal (including FDA post-approval) studies, society guidelines, independent expert opinion, and public comments.

    We conclude that the totality of evidence supports that IPAPS devices are a promising diagnostic technology which, when used consistently as part of a holistic, combined patient/care team approach to HF management, could lead to meaningful improvement of health outcomes for certain Medicare beneficiaries with HF. However, important questions remain, such as:

    • Can the improved health outcomes seen in trials be replicated in the real world, with a community-based, HF expert-led team remotely managing these patients in their homes, whether in an urban, rural or other setting?
    • Can the coordination required among the remote care team members, and with the patient/care giver at home, be achieved operationally to ensure timely monitoring, reporting, assessment of reports, appropriate actions taken based on those assessments, all done consistently over time, and in the real world? If not, no benefit would likely accrue, and there would be no purpose for implanting the device.
    • Can meaningful benefit from use of IPAPS be seen for the various subpopulations discussed above?
    • For all populations, can benefit be demonstrated over a longer period of time? This is an important consideration as these devices are implanted for life.

    We believe CED is the most appropriate NCD policy for IPAPS systems because it simultaneously covers this technology while collecting and analyzing more data to fill evidence gaps to answer key questions. In the past, CMS developed overarching CED study questions to guide CED study protocol development. For this DM, we provide specific CED study protocol criteria (i.e., Section I B 3 a-e) that guide how we expect protocols to address the remaining questions in the evidence base.

    We propose CED for IPAPS used in HF management of Medicare beneficiaries for FDA market-authorized indications with the following criteria for patients, physicians, and CMS-approved study protocols.

    General Rationale:  The below criteria derive from trials, expert opinion, and public comments.  Based on the totality of evidence reviewed in this NCD analysis, we believe all of these criteria are needed in CED studies to confidently answer whether Medicare beneficiaries are able to achieve improved health outcomes from use of an IPAPS system. 

    Patient Criteria

    Patients enrolled in a CMS-approved CED study must meet all of the following:

    (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).

    Rationale for (a): The FDA did not include an indication for NYHA Class I (asymptomatic) or Class IV (very symptomatic) patients (see Appendix C on NYHA Functional Classes). Trial evidence is stronger for NYHA Class III than for Class II. Trials have included patients regardless of LVEF, but secondary- and meta-analyses suggest that outcomes may vary depending on the patient’s LVEF. Thus, more evidence is needed for Class II patients, and for all patients across the LVEF spectrum.

    (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.

    Rationale for (b): The above criteria derive from recent trials reviewed. As is the standard, thresholds for elevated natriuretic peptides (B-type natriuretic peptides or BNP, or NT-proBNP) must be corrected for body mass index (BMI) for all LVEF ranges. We recognize that algorithms for BMI corrections and other methods may evolve. Thus, updated methods, as well as additional patient exclusion criteria, may be proposed in CED study protocol submissions.

    (c)  On guideline-directed medical therapy (GDMT) for at least 3 months with the goal of achieving optimal or maximally-tolerated GDMT 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)  Have access to reliable connectivity to ensure daily collection and submission of IPAPS data.

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

    Rationale for (c)-(g): We agree that CRT (with or without an ICD component) represents baseline standard of care for HF patients in need of one of these devices. The 3-month wait for CRT with or without an ICD component aligns with the 3-month wait for HF treatment with the standard of care, including GDMT; however, this is also done to avoid manipulation of the leads (as required in the MONITOR-HF trial).

    Candidates for IPAPS must be responsive to an adequate combination of major classes of GDMT the use of which IPAPS is intended to guide. Today, these classes include renin-angiotensin-aldosterone system (RAAS) inhibitors, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), angiotensin-neprilysin inhibitors (ARNi)), isosorbide dinitrate (ISDN), and beta-blockers. SGLT2 inhibitors are increasingly playing a role in HF with preserved EF as well as reduced EF. Patients must also be responsive to diuretics, and not have other conditions, such as a recent major cardiac or vascular event, that would render durable benefit from IPAPS unlikely. Patients must have daily access to reliable connectivity (e.g., wireless connectivity in the case of CardioMEMS) for the IPAPS system to work.

    Implantation must not occur during a hospital admission for an acute HF episode for multiple reasons (see our Response to Comments for extensive discussion). Of note: (i) the user manuals for CardioMEMS and Cordella require right heart catheterization to calibrate the device; the goal of the right heart catheterization is to calibrate the IPAPS when the patient has stable baseline parameters, and that is unlikely to happen during an inpatient stay for an acute HF episode. (ii) It is paramount that an outpatient cardiologist-led clinical team and plan are in place to manage the patient long term. (iii) The patient must meet the 3-month requirement for standard-of-care treatments, including GDMT. (iv) Allowing routine implantation directed by inpatient teams who are not accountable for consistent, long-term follow-up of the patient will not benefit Medicare beneficiaries with HF.

    Physician Criteria

    (a)  Physicians referring the above Medicare beneficiaries and managing them post implantation must be cardiologists with training and experience in HF management.

    (b)  Physicians implanting the device must have training and experience in pulmonary arterial catheterization and intervention.

    Rationale for (a) and (b): We do not require referring and post-implantation managing clinicians to be board-certified HF specialists because of limitations in the number and geographic distribution of such specialists. We anticipate further HF training programs, and perhaps certification, for other appropriate physicians, something we have seen in other fields of medicine to help overcome barriers to access. We believe the implantation procedure itself can be appropriately learned and performed by physicians who regularly perform similar procedures. To this end, clinical investigators designing CED study protocols may propose and justify training and proctoring requirements that would allow physicians with experience in similar procedures to meet the requirement for training and experience in pulmonary arterial catheterization and intervention.

    CED Study Criteria

    All CMS-approved CED studies must meet the patient and physician criteria above and include:

    (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.

    Rationale for (a):  Our focus on, and metrics for, HF hospitalizations derive from recent trials, independent expert opinion, and public comments.  While the primary metric for HF hospitalizations is the cumulative number at a minimum of 24 months, time-to-event analysis and total days in hospital (or the converse, days alive out of hospital) should also be reported.

    All-cause mortality is a core patient-centered outcome, accounts for competing causes of death without further adjudication, and appears in composite primary outcomes of reviewed trials along with HF hospitalizations.  The preponderance of evidence suggests that future studies may succeed in demonstrating reduction in HF hospitalizations but not in mortality; however, it is possible that decreased mortality is achievable for certain HF patients with reduced EF, as implied in a recent meta-analysis discussed above (Urban 2024).  The 24-month minimum period for CED studies expands evidence for durability of outcomes beyond past trials.

    Each component of a composite outcome must be individually reported to assess which component(s) is(are) driving the outcome.  For example, if a substantial reduction in a composite of all-cause mortality and HF hospitalizations were driven by the latter, and mortality actually increased slightly, that benefit (substantially decreased hospitalizations) and harm (slightly increased mortality) would be important for physicians and patients to know when making decisions.

    Finally, we are not requiring specific secondary outcomes, with the expectation that a number of these will inherently be included in CED study protocols.  For example, these might include, at a minimum, any hospitalization, any emergency room visit, cardiac mortality, and quality of life (e.g., Kansas City Cardiomyopathy Questionnaire).[7]

    (b) An active comparator.

    Rationale for (b):  Benefits and harms cannot be assessed without a comparator. An “active comparator” is inherent in RCTs that prospectively compare randomized intervention and control groups, but may be seen in other study designs, such as those employing propensity-score matching or instrumental variables. The latter studies can be many times larger than RCTs, and we believe can help fill in evidence gaps, especially for subgroups, left in the wake of the foundational but limited RCTs for IPAPS.

    (c) A care management plan that:

    • identifies members, roles and responsibilities of the HF expert-led clinical team 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.

    Rationale for (c):  In the trials that generated the promising evidence for IPAPS, patients were full participants in their own care and understood (through physician-patient shared decision making, or SDM) that consistent, long-term adherence to a care plan is needed to achieve beneficial outcomes.  This physician-patient SDM, and full patient participation, is needed in CED studies to replicate those trial results.  A medication management protocol provides evidence-based guidance that physicians and care teams will use when tracking patient data trends and tailoring interventions to the individual patient.  The entire care plan developed by study investigators and embedded in CED study protocols would provide an evidence-based roadmap for real-world clinical care after CED studies are completed.  

    (d) Design sufficient to demonstrate clinical utility of the device 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.

    Rationale for (d):  This is to ensure that patient benefits are due specifically to changes in medication informed by the continuous PA pressure data, and not due to other factors.

    (e)  Design sufficient for subgroup analyses by:

    • CRT-P, CRT-D, or ICD (with hemodynamic monitoring capabilities) 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.

    Rationale for (e):  More evidence is needed about the above subgroups to determine which patients will clinically benefit from IPAPS. Note that patients with advanced renal disease, including on dialysis, were excluded from trials. We do not exclude these patients from CED studies, but instead require subgroup analysis of them, because this is a core Medicare subpopulation. Many patients without renal failure who will receive an IPAPS (which remains implanted for life) will progress to renal failure, and through this CED study physicians will have more data to guide their appropriate management. Likewise, we expect many patients to advance to NYHA Class IV HF and do not want to exclude these patients from monitoring if a device has already been implanted. We anticipate studies would capture the impact of IPAPS for HF management on all of these subgroups.

    A CED study would be considered successful if it demonstrated:

    (1) That patient benefits are due specifically to changes in medication informed by the continuous PA pressure data, and not due to other factors such as intensive care team contact and guidance, and clinical decision making that could have been made based on clinical and laboratory factors other than PA pressure; and

    (2) A clinically meaningful improvement of the primary outcome in patients with IPAPS-guided HF treatment compared to similar patients treated without IPAPS-guided information.

    (a) A substantial reduction in HF hospitalizations alone for the treatment arm, with a decrease or no change in all-cause mortality, compared to the control, would be sufficient.

    (b) A substantial comparative decrease in HF hospitalizations without a corresponding increase in non-HF hospitalizations would be further reassuring.

    Our initial literature search and review of the evidence on the clinical utility of IPAPS for Medicare beneficiaries with HF were guided by three general questions. Answers to these questions inform the overarching question of whether IPAPS meets the reasonable and necessary standard under § 1862(a)(1)(A) of the Act.

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

    A1: No. Based on analysis of the available evidence, CMS finds that IPAPS for HF management do not meaningfully improve health outcomes for Medicare beneficiaries and therefore, is not reasonable and necessary under § 1862(a)(1)(A) of the Act because critical evidentiary gaps remain. The key RCTs and other studies make the case that a substantial reduction in HF hospitalizations represents a meaningful improvement in a patient-centered health outcome. However, due to the limitations in trials for IPAPS to date (as discussed in the Evidence Review and CMS Coverage Analysis sections above), the evidence that IPAPS causes a meaningful reduction in HF hospitalizations is suggestive, but not definitive.

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

    A2: Uncertain. That is, there is a great deal of uncertainty, due in part to small numbers of patients and wide confidence intervals surrounding their trial outcomes, as to whether use of an IPAPS device improves health outcomes for patients who are: over age 75 years, women, members of non-white race/ethnic groups, with preserved or mid-range LVEF (vs. reduced LVEF), NYHA Class II (vs III), with stage IV or greater chronic kidney disease, with a CRT and/or ICD device already implanted, or selected on the basis of lab parameters (e.g., BNP) rather than recent history of HF hospitalization. Based on the lack of evidence of a benefit for patients with co-morbidities and patient sub-groups, CED under §1862(a)(1)(E), is appropriate for IPAPS for HF management. We believe CMS-approved clinical studies could fill these gaps in the existing evidence base regarding appropriateness for the subgroups of Medicare beneficiaries listed above.

    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?

    A3: Uncertain. There is little evidence to date that outcomes achieved in rigorous trials at highly selective sites can be replicated in the real world, with a community-based, HF expert-led team remotely managing patients who reflect the diversity of the Medicare population. Based on the totality of the evidence, CMS finds further justification that coverage under CED is appropriate. We believe that CMS-approved clinal studies could fill these gaps in the evidence base regarding clinical utility of IPAPS for HF management for Medicare beneficiaries.

    For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in §1812 (Scope of Part A); §1832 (Scope of Part B); or §1861(s) (Definition of Medical and Other Health Services) of the Act.

    Implanted PAP sensor for heart failure management systems qualify as:

    • Inpatient hospital services
    • Outpatient hospital services
    • Physicians’ services

    Note: This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service.

    CMS will carefully monitor treated patients for adherence to the NCD criteria and will assess patient outcomes through evidence published in the peer-reviewed medical literature.  CMS will consider modifying this NCD contingent upon real-world demonstration of improved health outcomes for Medicare beneficiaries with HF, as described above.

    CMS recognizes the importance of shared decision-making (SDM) in many clinical scenarios and has required shared decision making in other NCDs (for example, implantable cardiac defibrillators: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx? NCDId=110 Opens in a new window).  CMS supports clinician-patient SDM for IPAPS for HF management, but recognizes that there is no fully developed tool available at this time.  CMS strongly encourages standardized decision aids or tools.  The National Quality Forum (NQF) has published standards for decision aids (www.qualityforum.org/Projects/c-d/Decision_Aids/Final_Report.aspx) to facilitate the decision-making process between a patient and clinician and will be monitoring this space closely.

    V.             History of Medicare Coverage

    At this time, coverage of IPAPS for HF management is at the discretion of Medicare Administrative Contractors (MAC)s.

    This is CMS’ first NCA on IPAPS for HF management. This request for coverage was externally initiated.  CMS received a complete, formal request to open an NCA on the topic of IPAPS for HF management from Abbott.  The request letter is available at https://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id313.pdf Opens in a new window

    Date Milestone

    April 30, 2024

    CMS posts a tracking sheet announcing the opening of the NCA. The first 30-day public comment period begins.

    May 30, 2024

    First public comment period ends.  CMS receives 462 comments.

    October 30, 2024

    CMS posts proposed Decision Memorandum.  Second 30-day public comment period begins.

    November 29, 2024

    Second public comment period ends. 

    January XX, 2025

    CMS posts final Decision Memorandum.

    VI.          Appendices

    The Centers for Medicare & Medicaid Services (CMS) covers 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.

    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 guideline-directed medical therapy (GDMT) for at least 3 months with the goal of achieving optimal or maximally-tolerated GDMTprior 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)   Have access to reliable connectivity to ensure daily collection and submission of IPAPS data.

    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 training and experience in HF management.

    b)      Physicians implanting an IPAPS must have 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-P, CRT-D, or ICD (with hemodynamic monitoring capabilities) 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)       CMS-approved CED studies must adhere to the following 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 Opens in a new window, 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 underrepresented 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.

    1.      IPAPS for HF management is not covered for patients outside of a CMS-approved study.

    2.      Nothing in this NCD would preclude coverage of IPAPS for HF management through NCD 310.1 (Clinical Trial Policy) or through the Investigational Device Exemption (IDE) Policy.

    CardioMEMS

    Table 1. Update Literature Search Strategy Performed in PubMed & Embase on February 13, 2024

    Search number Query Results

    13

    (#4 AND #9 AND #10 AND #11) NOT #12

    63

    12

    (("Animals"[MESH] OR "Animal Experimentation"[MESH] OR "Models, Animal"[MESH] OR "Vertebrates"[MESH]) NOT ("Humans"[MESH] OR "Human experimentation"[MESH]))

    5,194,818

    11

    English[Language]

    31,991,633

    10

    ("2022/12/01"[Date - Publication] : "2024"[Date - Publication]) 1,988,023

    9

    #5 OR #6 OR #7 OR #8

    10,577,073

    8

    "systematic"[filter] OR "meta-analysis"[pt] OR "meta-analysis as topic"[mh] OR "meta analy*"[tw] OR metanaly*[tw] OR metaanaly*[tw] OR "met analy*"[tw] OR "integrative research"[tiab] OR "integrative review*"[tiab] OR "integrative overview*"[tiab] OR "research integration*"[tiab] OR "research overview*"[tiab] OR "collaborative review*"[tiab] OR "collaborative overview*"[tiab] OR "systematic review"[pt] OR "systematic reviews as topic"[mh] OR "systematic review*"[tiab] OR "technology assessment*"[tiab] OR "technology overview*"[tiab] OR "technology appraisal*"[tiab] OR "Technology Assessment, Biomedical"[mh] OR HTA[tiab] OR HTAs[tiab] OR "comparative efficacy"[tiab] OR "comparative effectiveness"[tiab] OR "outcomes research"[tiab] OR "indirect comparison*"[tiab] OR "Bayesian comparison"[tiab] OR (("indirect treatment"[tiab] OR "mixed-treatment"[tiab]) AND comparison*[tiab]) OR Embase*[tiab] OR Cinahl*[tiab] OR "systematic overview*"[tiab] OR "methodological overview*"[tiab] OR "methodologic overview*"[tiab] OR "methodological review*"[tiab] OR "methodologic review*"[tiab] OR "quantitative review*"[tiab] OR "quantitative overview*"[tiab] OR "quantitative synthes*"[tiab] OR "pooled analy*"[tiab] OR Cochrane[tiab] OR Medline[tiab] OR Pubmed[tiab] OR Medlars[tiab] OR handsearch*[tiab] OR "hand search*"[tiab] OR "meta-regression*"[tiab] OR metaregression*[tiab] OR "data synthes*"[tiab] OR "data extraction"[tiab] OR "data abstraction*"[tiab] OR "mantel haenszel"[tiab] OR peto[tiab] OR "der-simonian"[tiab] OR dersimonian[tiab] OR "fixed effect*"[tiab] OR "multiple treatment comparison"[tiab] OR "mixed treatment meta-analys*"[tiab] OR "umbrella review*"[tiab] OR (("multiple paramet*"[tiab]) AND ("evidence synthesis"[tiab])) OR (("multi-paramet*"[tiab]) AND ("evidence synthesis"[tiab])) OR ((multiparameter*[tiab]) AND ("evidence synthesis"[tiab])) OR "Cochrane Database Syst Rev"[Journal] OR "health technology assessment winchester, england"[Journal] OR "Evid Rep Technol Assess (Full Rep)"[Journal] OR "Evid Rep Technol Assess (Summ)"[Journal] OR "Int J Technol Assess Health Care"[Journal] OR "GMS Health Technol Assess"[Journal] OR "Health Technol Assess (Rockv)"[Journal] OR "Health Technol Assess Rep"[Journal]

    687,764

    7

    "Cohort Studies"[Mesh] OR cohort*[Title/Abstract] OR "Controlled Clinical Trial" [Publication Type] OR ("Epidemiologic Methods"[Mesh:NoExp] AND ("1966"[Date - Publication] : "1989"[Date - Publication])) OR "Case-Control Studies"[Mesh] OR (case*[Title/Abstract] AND control*[Title/Abstract]) OR (case*[Title/Abstract] AND series[Title/Abstract]) OR "Case Reports" [Publication Type] OR "case report"[Title/Abstract:~2] OR "cases report"[Title/Abstract:~2] OR "case reports"[Title/Abstract:~2] OR "cases reports"[Title/Abstract:~2] OR "case reporting"[Title/Abstract:~2] OR "cases reporting" Title/Abstract:~2] OR "case reported"[Title/Abstract:~2] OR "cases reported"[Title/Abstract:~2] OR "case study"[Title/Abstract:~2] OR "case studies"[Title/Abstract:~2] OR "case studied"[Title/Abstract:~2] OR "case studying"[Title/Abstract:~2] OR "cases study"[Title/Abstract:~2] OR "cases studies"[Title/Abstract:~2] OR "cases studied"[Title/Abstract:~2] OR "cases studying"[Title/Abstract:~2]

    6,743,863

    6

    "Epidemiologic Studies"[Mesh:NoExp] OR "Case-Control Studies"[Mesh] OR "Cohort Studies"[Mesh] OR "case control"[Text Word] OR "cohort study"[Title/Abstract:~1] OR "cohort studies"[Title/Abstract:~1] OR "cohort study"[Text Word] OR "cohort studies"[Text Word] OR "cohort analy*"[Text Word] OR "follow up study"[Title/Abstract:~1] OR "follow up studies"[Title/Abstract:~1] OR "follow up study"[Text Word] OR "follow up studies"[Text Word] OR "observational study"[Title/Abstract:~1] OR "observational studies"[Title/Abstract:~1] OR "observational study"[Text Word] OR "observational studies"[Text Word] OR longitudinal[Text Word] OR retrospective[Text Word] OR "cross sectional"[Text Word] OR "Cross-Sectional Studies"[Mesh] OR "cohort study"[Title/Abstract:~1] OR "cohort studies"[Title/Abstract:~1] OR "cohort study"[Text Word] OR "cohort studies"[Text Word] OR cohort-analy*[Text Word] OR "follow up study"[Title/Abstract:~1] OR "follow up studies"[Title/Abstract:~1] OR "follow up study"[Text Word] OR "follow up studies"[Text Word] OR "observational study"[Title/Abstract:~1] OR "observational studies"[Title/Abstract:~1] OR "observational study"[Text Word] OR "observational studies"[Text Word] OR longitudinal[Text Word] OR retrospective[Text Word] OR "cross sectional"[Text Word] OR "case control"[ot] OR "cohort study"[ot] OR "cohort studies"[ot] OR cohort-analy*[ot] OR "follow up study"[ot] OR "follow up studies"[ot] OR "observational study"[ot] OR "observational studies"[ot] OR longitudinal[ot] OR retrospective[ot] OR "cross sectional"[ot]

    3,977,768

    5

    "Randomized Controlled Trial"[pt] OR "Controlled Clinical Trial"[pt] OR "Pragmatic Clinical Trial"[pt] OR "Equivalence Trial"[pt] OR "Clinical Trial, Phase III"[pt] OR "Randomized Controlled Trials as Topic"[mh] OR "Controlled Clinical Trials as Topic"[mh] OR "Random Allocation"[mh] OR "Double-Blind Method"[mh] OR "Single-Blind Method"[mh] OR Placebos[Mesh:NoExp] OR "Control Groups"[mh] OR (random*[tiab] OR sham[tiab] OR placebo*[tiab]) OR ((singl*[tiab] OR doubl*[tiab]) AND (blind*[tiab] OR dumm*[tiab] OR mask*[tiab])) OR ((tripl*[tiab] OR trebl*[tiab]) AND (blind*[tiab] OR dumm*[tiab] OR mask*[tiab])) OR (control*[tiab] AND (study[tiab] OR studies[tiab] OR trial*[tiab] OR group*[tiab])) OR (Nonrandom*[tiab] OR "non random*"[tiab] OR "non-random*"[tiab] OR "quasi-random*"[tiab] OR quasirandom*[tiab]) OR allocated[tiab] OR (("open label"[tiab] OR "open-label"[tiab]) AND (study[tiab] OR studies[tiab] OR trial*[tiab])) OR ((equivalence[tiab] OR superiority[tiab] OR "non-inferiority"[tiab] OR noninferiority[tiab]) AND (study[tiab] OR studies[tiab] OR trial*[tiab])) OR ("pragmatic study"[tiab] OR "pragmatic studies"[tiab]) OR ((pragmatic[tiab] OR practical[tiab]) AND trial*[tiab]) OR quasiexperimental[tiab] OR "quasi-experimental"[tiab]) AND (study[tiab] OR studies[tiab] OR trial*[tiab])) OR (phase[ti] AND (III[ti] OR 3[ti]) AND (study[ti] OR studies[ti] OR trial*[ti])) OR (phase[ot] AND (III[ot] OR 3[ot]) AND (study[ot] OR studies[ot] OR trial*[ot]))

    4,496,363

    4

    #1 AND (#2 OR #3)

    973

    3

    (implant*[Title/Abstract] OR invasive*[Title/Abstract]) AND ("Blood Pressure Monitoring, Ambulatory"[Mesh:NoExp] OR "Hemodynamic Monitoring"[Mesh:NoExp] OR "Hemodynamics"[Mesh:NoExp] OR (("Ambulatory Blood"[Title/Abstract] OR self[Title/Abstract] OR home[Title/Abstract]) AND "Pressure Monitor*"[Title/Abstract]) OR Hemodynamic* OR haemodynamic* OR "cardiovascular measurement*"[Title/Abstract] OR "cardiovascular monitor*"[Title/Abstract] OR "24 hour blood pressure"[Title/Abstract] OR "24-hour blood pressure"[Title/Abstract] OR "blood pressure monitoring"[Title/Abstract]) AND ("Pulmonary Artery"[Mesh:NoExp] OR "Pulmonary Arter*"[Title/Abstract] OR "arterial pulmonary pressure*"[Title/Abstract] OR "intrapulmonary pressure*"[Title/Abstract] OR "pulmonary arterial pressure*"[Title/Abstract] OR "pulmonary artery pressure*"[Title/Abstract] OR "pulmonary blood pressure*"[Title/Abstract])

    2,991

    2

    CardioMEMS[Title/Abstract]

    193

    1

    "Heart Failure"[Mesh:NoExp] OR "Heart Failure"[Title/Abstract:~3] OR "heart decompensation"[Title/Abstract:~3] OR "heart incompetence"[Title/Abstract:~3] OR "heart insufficiency"[Title/Abstract:~3] OR "cardiac decompensation"[Title/Abstract:~3] OR "cardiac failure"[Title/Abstract:~3] OR "cardiac incompetence"[Title/Abstract:~3] OR "cardiac insufficiency"[Title/Abstract:~3] OR "cardiac stand still"[Title/Abstract:~3] OR "cardial decompensation"[Title/Abstract:~3] OR "cardial insufficiency"[Title/Abstract:~3] OR "decompensatio cordis"[Title/Abstract:~3] OR "insufficientia cardis"[Title/Abstract:~3] OR "myocardial failure"[Title/Abstract:~3] OR "myocardial insufficiency"[Title/Abstract:~3]

    281,976


    Table 2. Inclusion and Exclusion Criteria

    PICOTS Element Inclusion Criteria Exclusion Criteria
    Populations NYHA Class II or III HF patients who either:

    • have been hospitalized for HF in the previous year and/or
    • have elevated natriuretic peptides
    Population other than FDA label indication
    Intervention CardioMEMS Heart Failure System (Abbott) - Remote Implantable Hemodynamic Monitoring Other than CardioMEMS (Abbott)
    Comparators Any or None N/A
    Outcomes Efficacy:
    • ∆ in HF Hospitalizations
    • ∆ in PA pressure
    • QoL (KCCQ, EQ-5D-5L, PHQ-9, MLWHFQ)
    Safety:
    Device- or system-related adverse events
     
    Timing Any N/A
    Setting Any N/A

    Study design

    • RCT
    • Observational study
    • Systematic Review/Meta-analysis

    N< 100

    Publications

    • English-language publications 
    • Published 2004 – present (2022; original)
    • Published 2022 - 2024 
  • Non-English language publications
  • Non-clinical study (e.g. narrative review, commentary, editorial)
  • Abstracts, conference proceedings, gray literature, non-clinical studies

  • Table 3. Studies Excluded Due to Sample Size ≤100 Patients 

    Reference n

    2004 - 2022

    Abraham, W. T., Adamson, P. B., Hasan, A., Bourge, R. C., Pamboukian, S. V., Aaron, M. F., & Raval, N. Y. (2011). Safety and accuracy of a wireless pulmonary artery pressure monitoring system in patients with heart failure. Am Heart J, 161(3), 558-566. https://doi.org/10.1016/j.ahj.2010.10.041

    17

    Assaad, M., Singh, R., Sarsam, S., Bowen, A., & Zughaib, M. (2018). Impact of CardioMEMS device placement on lifestyle modifications: a "pseudo-placebo" effect beyond the expected? J Int Med Res, 46(8), 3195-3199. https://doi.org/10.1177/0300060518774123

    30

    Codina, P., Altisent, O. A., Santiago-Vacas, E., Domingo, M., Lupon, J., & Bayes-Genis, A. (2021). A new option for monitoring heart failure. First experience in Spain with CardioMEMS. Med Clin (Barc), 156(1), 26-28. https://doi.org/10.1016/j.medcli.2020.07.028

    11

    Jermyn, R., Alam, A., Kvasic, J., Saeed, O., & Jorde, U. (2017). Hemodynamic-guided heart-failure management using a wireless implantable sensor: Infrastructure, methods, and results in a community heart failure disease-management program. Clin Cardiol, 40(3), 170-176. https://doi.org/10.1002/clc.22643

    66

    Milligan, G. P., Minniefield, N., Raju, B., Patel, N., Michelis, K., Van Zyl, J., Cheeran, D., & Alam, A. (2022). Effectiveness and Safety Profile of Remote Pulmonary Artery Hemodynamic Monitoring in a "Real-World" Veterans Affairs Healthcare System. Am J Cardiol, 184, 56-62. https://doi.org/10.1016/j.amjcard.2022.08.039

    53

    Sager, D. M., Burch, A. E., Alhosaini, H., Vaughan, T., & Sears, S. F. (2020). Changes in cardiac anxiety and self-care practices in heart failure patients following implantation of wireless hemodynamic monitoring sensors. Eur J Cardiovasc Nurs, 19(5), 440-443. https://doi.org/10.1177/1474515120905405

    26

    Vaz Ferreira, V., Pereira-da-Silva, T., Cacela, D., & Cruz Ferreira, R. (2022). Remote invasive monitoring of pulmonary artery pressures in heart failure patients: Initial experience in Portugal in the context of the Covid-19 pandemic. Rev Port Cardiol, 41(5), 381-390. https://doi.org/10.1016/j.repc.2021.06.016

    5

    2022 - 2024

    Aggarwal, A., Khan, Z., Machado, C., & Zughaib, M. (2023). Assessing Correlation Between Thoracic Impedance and Remotely Monitored Pulmonary Artery Pressure in Chronic Systolic Heart Failure. Cardiol Res, 14(1), 32-37. https://doi.org/10.14740/cr1447

    9

    Angullo-Gomez, M., Robles-Mezcua, A., Becerra-Munoz, V. M., & Garcia-Pinilla, J. M. (2022). Case report on ambulatory pulmonary pressure monitoring: an attempt to reduce readmissions for heart failure with preserved ejection fraction. Eur Heart J Case Rep, 6(10), ytac401. https://doi.org/10.1093/ehjcr/ytac401

    1

    Bhat, D. P., Graziano, J. N., Garn, B. J., & Franklin, W. J. (2023). Safety and utility of CardioMEMS device for remote pulmonary artery monitoring in paediatric Fontan patients: a case series. Eur Heart J Case Rep, 7(9), ytad422. https://doi.org/10.1093/ehjcr/ytad422

    8

    Chilcote, J. L., Summers, R. P., Vaz, D. G., Barber, R., Wariar, R., & Guichard, J. L. (2022). Concurrent Assessment of the CardioMEMS HF System and HeartLogic HF Diagnostic: A Retrospective Case Series. J Card Fail, 28(1), 44-55. https://doi.org/10.1016/j.cardfail.2021.07.010

    7

    Codina, P., Domingo, M., Barcelo, E., Gastelurrutia, P., Casquete, D., Vila, J., Abdul-Jawad Altisent, O., Spitaleri, G., Cediel, G., Santiago-Vacas, E., Zamora, E., Ruiz-Cueto, M., Santesmases, J., de la Espriella, R., Pascual-Figal, D. A., Nunez, J., Lupon, J., & Bayes-Genis, A. (2022). Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension. ESC Heart Fail, 9(4), 2170-2180. https://doi.org/10.1002/ehf2.13952

    14

    Dannenberg, V., Koschutnik, M., Dona, C., Nitsche, C., Spinka, G., Heitzinger, G., Mascherbauer, K., Kammerlander, A., Schneider-Reigbert, M., Winter, M. P., Bartko, P., Goliasch, G., Hengstenberg, C., Mascherbauer, J., & Gwechenberger, M. (2023). Monitoring of mitral- and tricuspid valve interventions with CardioMEMS: Insights beyond imaging. Eur J Clin Invest, 53(6), e13961. https://doi.org/10.1111/eci.13961

    36

    Dauw, J., Sokolski, M., Middleton, J. T., Nijst, P., Dupont, M., Forouzan, O., Rothman, A. M. K., Ruschitzka, F., Flammer, A. J., & Mullens, W. (2022). Ambulatory haemodynamic-guided management reduces heart failure hospitalizations in a multicentre European heart failure cohort. ESC Heart Fail, 9(6), 3858-3867. https://doi.org/10.1002/ehf2.14056

    29

    Garg, T., Raikhelkar, J., Gilkeson, R., & Tavri, S. (2022). Large pulmonary artery pseudoaneurysm after CardioMEMS implantation: a case report. Eur Heart J Case Rep, 6(4), ytac113. https://doi.org/10.1093/ehjcr/ytac113

    1

    Gibson, J., McGrath, K., Miller, R. J. H., Sumner, G., & Clarke, B. (2023). Ambulatory Pulmonary Artery Pressure Monitoring Reduces Costs and Improves Outcomes in Symptomatic Heart Failure: A Single-Centre Canadian Experience. CJC open, 5(3), 237-249. https://doi.org/10.1016/j.cjco.2022.12.008

    20

    Kelly, R., Bae, J. Y., Mansour, A. Y., Nagpal, S., Hahn, S., & Murugiah, K. (2023). Wireless pulmonary artery sensor implantation in a unilateral lung transplant recipient. J Cardiol Cases, 28(5), 216-220. https://doi.org/10.1016/j.jccase.2023.08.004

    1

    Khan, M. S., Khouri, M. G., Gomez, L., & Fudim, M. (2023). Pressures do not equal volumes: implications for heart failure management in patients with CardioMEMS. ESC Heart Fail, 10(1), 716-720. https://doi.org/10.1002/ehf2.14219

    2

    Khedraki, R., Abraham, J., Jonsson, O., Bhatt, K., Omar, H. R., Bennett, M., Bhimaraj, A., Guha, A., McCann, P., Muse, E. D., Robinson, M., Sauer, A. J., Cheng, A., Bagsic, S., Fudim, M., Heywood, J. T., & Guglin, M. (2023). Impact of exercise on pulmonary artery pressure in patients with heart failure using an ambulatory pulmonary artery pressure monitor. Front Cardiovasc Med, 10, 1077365. https://doi.org/10.3389/fcvm.2023.1077365

    66

    Kittipibul, V., Yaranov, D. M., Jefferies, J. L., Silver, M. A., Burkhoff, D., Rao, V. N., Biegus, J., Ponikowski, P., & Fudim, M. (2023). Pressure-Volume Profiles in Heart Failure Across Sexes and Phenotypes. J Cardiovasc Transl Res, 16(3), 751-753. https://doi.org/10.1007/s12265-022-10345-7

    20

    Marshall, W. H. t., Rajpal, S., Mah, M. L., Armstrong, A. K., Salavitabar, A., Hickey, J., Metzger, R., Sisk, T., & Daniels, C. J. (2023). Early Experience and Lessons Learned Using Implanted Hemodynamic Monitoring in Patients With Fontan Circulation. J Am Heart Assoc, 12(24), e031836. https://doi.org/10.1161/JAHA.123.031836

    18

    Nassif, M. E., Nguyen, D., Spertus, J. A., Gosch, K. L., Tang, F., Windsor, S. L., Jones, P., Khariton, Y., Sauer, A. J., & Kosiborod, M. N. (2023). Association Between Change in Ambulatory Pulmonary Artery Pressures and Natriuretic Peptides in Patients with Heart Failure: Results From the EMBRACE-HF Trial. J Card Fail, 29(9), 1324-1328. https://doi.org/10.1016/j.cardfail.2023.05.009

    62

    Orr, W. B., Colombo, J. N., Roberts, B., Silva, J. N. A., & Balzer, D. (2022). Incorporation of the CardioMEMS System During an Exercise Physiology Test in a Pediatric Congenital Heart Disease Patient Contributing to Medical Decision-Making. Pediatr Cardiol, 43(3), 695-699. https://doi.org/10.1007/s00246-021-02758-z

    1

    Sethi, P., Acharya, P., Lancaster, P., Stack, B., Munshi, K., Ranka, S., Shah, Z., Sauer, A. J., & Gupta, K. (2023). Orthostatic variation of pulmonary artery pressure in ambulatory heart failure patients. BMC Cardiovasc Disord, 23(1), 503. https://doi.org/10.1186/s12872-023-03534-y

    30

    Sethi, P., Lancaster, P., Stack, B., Steinkamp, L., Acharya, P., Munshi, K., Hockstad, E., Shah, Z., Sauer, A. J., & Gupta, K. (2023). Diurnal variation of pulmonary artery pressure in ambulatory heart failure patients. Acta Cardiol, 78(2), 256-259. https://doi.org/10.1080/00015385.2022.2101777

    17

    Visco, V., Esposito, C., Manzo, M., Fiorentino, A., Galasso, G., Vecchione, C., & Ciccarelli, M. (2022). A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS. Front Cardiovasc Med, 9, 874433. https://doi.org/10.3389/fcvm.2022.874433

    1

    Zheng, L., Smith, N. J., Teng, B. Q., Szabo, A., & Joyce, D. L. (2022). Predictive Model for Heart Failure Readmission Using Nationwide Readmissions Database. Mayo Clin Proc Innov Qual Outcomes, 6(3), 228-238. https://doi.org/10.1016/j.mayocpiqo.2022.04.002

    34


    Table 4. RCT Study Participant Exclusion Criteria

    CHAMPION (Abraham et al., 2011) GUIDE-HF (Lindenfeld et al., 2021) MONITOR-HF (Brugts et al., 2023)

    Patients with history of recurrent (> 1) pulmonary embolism or deep vein thrombosis

    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)

    Patients with an active infection.

    Patients, in the Investigator's opinion, unable to tolerate a right heart catheterization

    ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes)

    Patients with history of recurrent (>1) pulmonary embolism or deep vein thrombosis.

    Patients who have had a major cardiovascular event (e.g., myocardial infarction, stroke) within 2 months of Screening Visit

    Received or are likely to receive an advanced therapy (e.g., mechanical circulatory support or cardiac transplant) in the next 12 months

    Patients who have had a major cardiovascular event (e.g., myocardial infarction, open heart surgery, stroke) within 2 months.

    Patients with Cardiac Resynchronization Device implanted ≤ 3 months prior to enrollment

    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

    Patients with Cardiac Resynchronization Therapy device (CRT) implanted <3 months prior to enrolment and implantation of the sensor (in order to avoid manipulation of the lead).

    Patients with a Glomerular Filtration Rate <25 ml/min who are non-responsive to diuretic therapy or who are on chronic renal dialysis

    Glomerular Filtration Rate < 25 mL/min and non-responsive to diuretic therapy, or receiving chronic dialysis

    Patients with a Glomerular Filtration Rate <25 ml/min (obtained within 2 weeks of the baseline visit), refractory to diuretic therapy, or on chronic renal dialysis.

    Patients likely to undergo heart transplantation within 6 months of Screening visit

    Inability to tolerate or receive dual antiplatelet therapy or anticoagulation therapy for one month post-implantation

    Patients with complex congenital heart disease or mechanical right heart valve(s).

    Patients with congenital heart disease or mechanical right heart valve(s)

    Significant congenital heart disease that has not been repaired and would prevent implantation of the CardioMEMS™ PA Sensor

    Patients with known pulmonary arterial hypertension (WHO category 1 or 4/5) were PA pressure are most likely not responsive to cardiac treatment.

    Patients with known coagulation disorders

    Implanted with mechanical right heart valve(s)

    Patients scheduled for or likely to undergo heart-transplantation or VAD within 6 months of baseline visit.

    Patients with a hypersensitivity or allergy to aspirin, and/or clopidogrel

    Unrepaired severe valvular disease

    Patients with known coagulation disorders or allergy to aspirin, and/or lopidogrel

     

    Pregnant or planning to become pregnant in the next 12 months

     

     

    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).

     

     

    History of current or recurrent (≥ 2 episodes within 5 years prior to consent) pulmonary emboli and/or deep vein thrombosis

     

     

    Major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary intervention, open heart surgery, or stroke, etc.) within 90 days prior to consent

     

     

    Implanted with Cardiac Resynchronization Therapy)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to consent

     

     

    Enrollment into another trial with an active treatment arm

     

     

    Anticipated life expectancy of < 12 months

     

     

    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 right heart catheterization, a history of non-compliance, or any condition that would preclude CardioMEMS™ PA Sensor implantation

     

    Cordella

    The population, interventions, comparators, outcomes, timing, and settings (PICOTS) are defined in Table 5 below: 

    Table 5. Inclusion and Exclusion Criteria 

    PICOTS Element Inclusion Criteria Exclusion Criteria

    Populations

    Patients who have/had NYHA Class I, II or III HF

    Population other than HF

    Intervention

    Cordella Heart Failure System

    Study that does not use Cordella Heart Failure System

    Comparators

    Any or None

     N/A

    Outcomes

    All efficacy and safety outcomes reported

     N/A

    Timing

    Any follow-up period

     N/A

    Setting

    US and OUS

     N/A

    Study design

    All study design types such as

  • RCT
  • Observational study
    Note: Relevant systematic reviews/meta-analyses will be used to supplement findings.
  • Narrative review, commentary or editorial

    Publications

  • English-language publications
  • Peer-reviewed publications
  • Non-English language publications
  • Animal or in-vitro study
  • Study protocols
  • Cost-effective analyses
  • Gray literature
  • Pre-clinical studies
  • Abbreviations: HF: Heart failure; N/A: not applicable; OUS: outside of US; RCT: Randomized controlled trial; US: United States 


    Table 6. Search strategy for PubMed and Embase (searches conducted on 2024-7-12)

    Search number Query Results

    Search strategy for PubMed (searches conducted on 2024-7-12)

     

    5

    (#1 AND (#3 OR #4)) OR (#2 AND #3 AND #4)

    17

    4

    (implant*[Title/Abstract] OR invasive*[Title/Abstract]) AND ("Blood Pressure Monitoring, Ambulatory"[Mesh:NoExp] OR "Hemodynamic Monitoring"[Mesh:NoExp] OR "Hemodynamics"[Mesh:NoExp] OR (("Ambulatory Blood"[Title/Abstract] OR self[Title/Abstract] OR home[Title/Abstract]) AND "Pressure Monitor*"[Title/Abstract]) OR Hemodynamic* OR haemodynamic* OR "cardiovascular measurement*"[Title/Abstract] OR "cardiovascular monitor*"[Title/Abstract] OR "24 hour blood pressure"[Title/Abstract] OR "24-hour blood pressure"[Title/Abstract] OR "blood pressure monitoring"[Title/Abstract]) AND ("Pulmonary Artery"[Mesh:NoExp] OR "Pulmonary Arter*"[Title/Abstract] OR "arterial pulmonary pressure*"[Title/Abstract] OR "intrapulmonary pressure*"[Title/Abstract] OR "pulmonary arterial pressure*"[Title/Abstract] OR "pulmonary artery pressure*" Title/Abstract] OR "pulmonary blood pressure*"[Title/Abstract])

    3,048

    3

    "Heart Failure"[Mesh:NoExp] OR "Heart Failure"[Title/Abstract:~3] OR "heart decompensation"[Title/Abstract:~3] OR "heart incompetence"[Title/Abstract:~3] OR "heart insufficiency"[Title/Abstract:~3] OR "cardiac decompensation"[Title/Abstract:~3] OR "cardiac failure"[Title/Abstract:~3] OR "cardiac incompetence"[Title/Abstract:~3] OR "cardiac insufficiency"[Title/Abstract:~3] OR "cardiac stand still"[Title/Abstract:~3] OR "cardial decompensation"[Title/Abstract:~3] OR "cardial insufficiency"[Title/Abstract:~3] OR "decompensatio cordis"[Title/Abstract:~3] OR "insufficientia cardis"[Title/Abstract:~3] OR "myocardial failure"[Title/Abstract:~3] OR "myocardial insufficiency"[Title/Abstract:~3]

    289,141

    2

    endotronix

    245

    1

    cordella

    382

    Search strategy for Embase (searches conducted on 2024-7-12)

     

    No.

    Query

    Results

    #3

    #1 OR #2

    25

    #2

    endotronix:df,ab,ti,kw

    6

    #1

    cordella:dn,ab,ti,kw

    23

    Table 7. Published References Reviewed 

    No. Reference

    1

    Mullens, W.,Sharif, F.,Dupont, M.,Rothman, A. M. K.,Wijns, W. (2020).  Digital health care solution for proactive heart failure management with the Cordella Heart Failure System: results of the SIRONA first-in-human study Eur J Heart Fail, 22(10), 1912-1919

    2

    Sharif, F.,Rosenkranz, S.,Bartunek, J.,Kempf, T.,Assmus, B.,Mahon, N. G.,Mullens, W. (2022).  Safety and efficacy of a wireless pulmonary artery pressure sensor: primary endpoint results of the SIRONA 2 clinical trial ESC Heart Fail, 9(5), 2862-2872

    3

    Sharif, F.,Rosenkranz, S.,Bartunek, J.,Kempf, T.,Aßmus, B.,Mahon, N. G.,Hiivala, N. J.,Mullens, W. (2024).  Twelve-month follow-up results from the SIRONA 2 clinical trial ESC Heart Fail, 11(2), 1133-1143

    4

    Guichard, J. L.,Cowger, J. A.,Chaparro, S. V.,Kiernan, M. S.,Mullens, W.,Mahr, C.,Mullin, C.,Forouzan, O.,Hiivala, N. J.,Sauerland, A.,Leadley, K.,Klein, L. (2023). Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System J Card Fail, 29(2), 171-180

    Table 8. References Excluded

    Reference Reason for Exclusion

    Anne Dual S, Nayak A, Hu Y, Schmid Daners M, Morris AA, Cowger J. Does Size Matter for Female Continuous-flow LVAD Recipients? A Translational Approach to a Decade Long Question. Asaio j. Jan 1 2022;68(1):21-27.

    Intervention not of interest

    Cordella C, Luebbers HT, Rivelli V, Grätz KW, Kruse AL. An evaluation of the preoperative hemoglobin level as a prognostic factor for oral squamous cell carcinoma. Article. Head and Neck Oncology. 2011;3(1)

    Intervention not of interest

    Donatello S, Cordella M, Kaps R, Kowalska M, Wolf O. Correction to: Are the existing eu ecolabel criteria for furniture products too complex? An analysis of complexity from a material and a supply chain perspective and suggestions for ways ahead (The International Journal of Life Cycle Assessment, (2020), 25, 5, (868-882), 10.1007/s11367-019-01601-1). Erratum. International Journal of Life Cycle Assessment. 2021;26(10):2103.

    Intervention not of interest

    Kundu GC, Mandal AK, Zhang Z, Mantile-Selvaggi G, Mukherjee AB. Uteroglobin (UG) suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins. Article. Journal of Biological Chemistry. 1998;273(35):22819-22824.

    Intervention not of interest

    Manavi T, Ijaz M, O'Grady H, et al. Design and Haemodynamic Analysis of a Novel Anchoring System for Central Venous Pressure Measurement. Sensors (Basel). Nov 6 2022;22(21)

    Narrative review

    Manavi T, Vazquez P, O'Grady H, et al. A novel wireless implant for central venous pressure measurement: First animal experience. Cardiovasc Digit Health J. Nov-Dec 2020;1(3):130-138.

    Animal study

    Mantile G, Miele L, Cordella-Miele E, Singh G, Katyal SL, Mukherjee AB. Human Clara cell 10-kDa protein is the counterpart of rabbit uteroglobin. Article. Journal of Biological Chemistry. 1993;268(27):20343-20351.

    Intervention not of interest

    Merad M, De Montalivet E, Legrand M, et al. Improving the control of prostheses in arm amputees with approaches based on motor coordination. Conference Abstract. Computer Methods in Biomechanics and Biomedical Engineering. 2019;22:S445-S447.

    Intervention not of interest

    Piccirillo G, Moscucci F, Sciomer S, Magrì D. Chronic Heart Failure Management: Monitoring Patients and Intercepting Exacerbations. Review. Reviews in Cardiovascular Medicine. 2023;24(7)

    Intervention not of interest

    Schneider D, Köhler K, Köhler F. [Telemedicine in cardiology - what is new?]. Dtsch Med Wochenschr. Jun 2023;148(12):767-773. Telemedizin in der Kardiologie – was ist neu?

    Intervention not of interest

    Terry M. NASA, telemedicine, and endotronix: how NASA's research led to the creation of a cutting-edge telemedicine company. Article. Telemedicine journal and e-health: the official journal of the American Telemedicine Association. 2010;16(5):528-532.

    Animal study

    Abraham WT, Perl L. Implantable Hemodynamic Monitoring for Heart Failure Patients. Review. Journal of the American College of Cardiology. 2017;70(3):389-398.

    Intervention not of interest

    Bekfani T, Fudim M, Cleland JGF, et al. A current and future outlook on upcoming technologies in remote monitoring of patients with heart failure. Review. European Journal of Heart Failure. 2021;23(1):175-185.

    Intervention not of interest

    Clephas PRD, Aydin D, Radhoe SP, Brugts JJ. Recent Advances in Remote Pulmonary Artery Pressure Monitoring for Patients with Chronic Heart Failure: Current Evidence and Future Perspectives. Sensors (Basel). Jan 26 2023;23(3)

    Outcomes not of interest

    Dauw J, Sokolski M, Middleton J, et al. #Ambulatory haemodynamic-guided management reduces heart failure hospitalisations in a multicentre European heart failure cohort. Conference Abstract. Acta Cardiologica. 2022;77:15-16.

    Narrative review

    Dauw J, Sokolski M, Middleton JT, et al. Ambulatory haemodynamic-guided management reduces heart failure hospitalizations in a multicentre European heart failure cohort. ESC Heart Fail. Dec 2022;9(6):3858-3867.

    Data not reported for Cordella separately

    Guichard JL, Sharif F, Forouzan O, Martina J, Klein L. A Procedural Guide for Implanting the Cordella Pulmonary Artery Pressure Sensor. J Invasive Cardiol. Feb 2023;35(2): E75-e83.

    Combined data reported for CardioMEMs and Cordella. Data not reported separately for Cordella.

    Heywood JT, Munshi K, Jordan T, et al. Multicenter registry and test bed for extended outpatient hemodynamic monitoring: the hemodynamic frontiers in heart failure (HF(2)) initiative. Front Cardiovasc Med. 2023; 10:1321415.

    Duplicate of ID 1

    Kobe EA, McVeigh T, Hameed I, Fudim M. Heart Failure Remote Monitoring: A Review and Implementation How-To. Review. Journal of Clinical Medicine. 2023;12(19)

    Narrative review

    Mortara A, Margonato D. Proactive management of heart failure by digital health: is monitoring of invasive pulmonary artery pressure the Holy Grail? Editorial. European Journal of Heart Failure. 2020;22(10):1920-1922.

    Narrative review

    Mullens W, Martens P, Forouzan O, et al. Effects of dapagliflozin on congestion assessed by remote pulmonary artery pressure monitoring. ESC Heart Fail. Oct 2020;7(5):2071-2073.

    Duplicate of ID 11

    Mullens W, Rosenkranz S, Sharif F, et al. Continuous Non-invasive Pulmonary Artery Pressure Monitoring In Heart Failure Patients Undergoing Submaximal Exercise. Conference Abstract. Journal of Cardiac Failure. 2024;30(1):299.

    Narrative review

    Nguyen Q, Luc JGY, Skarsgard PL. Highlights from the Transcatheter Cardiovascular Therapeutics 2021 meeting. Article. Artificial Organs. 2022;46(6):1204-1208.

    Narrative review

    Tedford RJ, Leacche M, Lorts A, Drakos SG, Pagani FD, Cowger J. Durable Mechanical Circulatory Support: JACC Scientific Statement. J Am Coll Cardiol. Oct 3, 2023;82(14):1464-1481.

    Intervention not of interest

    Zafar, H.,Neelam-Naganathan, D.,Middleton, J. T.,Binmahfooz, S. K.,Battersby, C.,Rogers, D.,Swift, A. J.,Rothman, A. M. K. (2023). Anatomical characterization of pulmonary artery and implications to pulmonary artery pressure monitor implantation Sci Rep, 13(1), 20528

    Outcome not of interest

    Appendix C.  New York Heart Association (NYHA) Functional Classification for Heart Failure

    Class

    Patient Symptoms

    I

    No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.

    II

    Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.

    III

    Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.

    IV

    Symptoms of heart failure at rest. Any physical activity causes further discomfort.

    American Heart Association, at https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure Opens in a new window (accessed Sept 5, 2024)


    [1] Clinical Trials.gov. Active comparator arm. Glossary. Last updated July 1, 2024. Available at: https://clinicaltrials.gov/study-basics/glossary Opens in a new window.Accessed October 22, 2024.

    [2] CMS’ CED Guidance Document (2024) Opens in a new window, 2, 3.

    [3] CMS’ CED Guidance Document (2024) Opens in a new window, 4

    [4] CMS’ CED Guidance Document (2024) Opens in a new window, 6.  This document also contains information on the purpose, principles, and process of CED.

    [5] Medical management protocols in MONITOR-HF had greater detail and standardization than, for instance, in GUIDE-HF (see the Supplementary Appendices for each trial).

    [6] “[I]t is challenging to expect that monitoring alone would reduce any endpoint because it merely provides information.  The crucial factor is what actions the physician takes based on this information.  So, if the primary intervention aimed at reducing PAP is an increase in diuretic dosage . . . it may not translate into a better prognosis [decreased mortality], as we know that diuretics do not themselves improve prognosis but rather alleviate clinical symptoms of congestion.  As demonstrated in the STRONG-HF study, the optimization of neurohormonal blockade [i.e., with GDMT] proves to be a safe strategy, irrespective of the patient’s age, comorbidities, or natriuretic peptide level (Chioncel 2023, Čerlinskaitė-Bajorė 2023, Arrigo 2023, Adamo 2023).  The development of a response algorithm to elevated PAP based not only on the escalation of the diuretics but rather, on the optimization of the guideline-directed medical therapy (GDMT) i.e. renin–angiotensin–aldosterone system (RAAS) blockade and sodium–glucose cotransporter 2 (SGLT-2) inhibitors, both of which possess decongestion-promoting properties, including indirect reductions in PAP, might yield more favourable outcomes (Biegus 2023, Nassif 2021, Biegus 2023b).  The absence of a positive effect on mortality may be attributed to the characteristics of the population included in the analysed trials, wherein a substantial proportion consisted of patients with HFpEF.  Given that individuals with HFpEF frequently experience non-cardiovascular mortality (Zile 2010), demonstrating a mortality reduction with a device in this particular population proves challenging” (Urban 2024).

    [7] Regarding secondary outcomes: Reporting of any hospitalization allows for calculation of non-HF hospitalizations.  As demonstrated in MONITOR-HF, it would be reassuring if there were a substantial decrease in HF hospitalizations, without a corresponding increase in non-HF hospitalizations.  This would support that the reduction reflects a true change in HF events, and not simply a change in the admitting diagnosis.  Note that many hospitalizations are for patients with heart failure, but not due primarily to their heart failure, necessitating clinical judgement calls.

    Cardiac mortality is a frequent trial outcome, although it is arguably more device-centered than all-cause mortality, which is more patient-centered (patients care most about whether they live or die, not why) and intrinsically accounts for competing causes of death without further adjudication. Quality of life is an important, patient-centered outcome, but is less accurately assessed in observational studies than in randomized trials (hence it is not typically a primary outcome for non-randomized CED studies).  Including this as a secondary outcome in CED studies, however, will assist in confirming quality of life metrics reported in the contemporary trials.

  • Bibliography