Medical Policy

Policy Num:      02.002.016
Policy Name:    Cardiac Hemodynamic Monitoring for the Management of Heart Failure in the Outpatient Setting

Policy ID:          [02.002.016]  [Ac / B / M- / P-]  [2.02.24]

Last Review:       July 16, 2024
Next Review:      July 20, 2025

Related Policies:

02.002.009- Biventricular Pacemakers (Cardiac Resynchronization Therapy) for the Treatment of Heart Failure

Cardiac Hemodynamic Monitoring for the Management of Heart Failure in the Outpatient Setting

Summary

Description

A variety of outpatient cardiac hemodynamic monitoring devices are intended to improve quality of life and reduce morbidity for patients with heart failure by decreasing episodes of acute decompensation. Monitors can identify physiologic changes that precede clinical symptoms and thus allow preventive intervention. These devices operate through various mechanisms, including implantable pressure sensors, thoracic bioimpedance measurement, inert gas rebreathing, and estimation of left ventricular end-diastolic pressure by arterial pressure during the Valsalva maneuver.

Summary of Evidence

For individuals with New York Heart Association (NYHA) class II-IV heart failure in outpatient settings who have had a hospitalization in the past year and/or have elevated natriuretic peptides who receive hemodynamic monitoring with an implantable pulmonary artery pressure sensor device, the evidence includes 2 meta-analyses, randomized controlled trials (RCTs), and nonrandomized studies. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. One implantable pressure monitor, the CardioMEMS device, has U.S. Food and drug Administration (FDA) approval. The pivotal CHAMPION RCT reported a statistically significant 28% decrease in heart failure hospitalization (HFH) in patients implanted with the CardioMEMS device compared with usual care. However, trial results were potentially biased in favor of the treatment group due to the use of additional nurse communication to enhance protocol compliance with the device. The manufacturer conducted multiple analyses to address potential bias from the nurse interventions. Results were reviewed favorably by the FDA. While these analyses demonstrated the consistency of benefit of the CardioMEMS device, all such analyses have methodologic limitations. Early safety data have been suggestive of a higher rate of procedural complications, particularly related to pulmonary artery injury. While the U.S. CardioMEMS post-approval study and CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) study reported a significant decrease in HFH with few device- or system-related complications at 1 year, the impact of nursing interventions remains unclear. The subsequent GUIDE-HF RCT failed to meet its primary efficacy endpoint, the composite of HFH, urgent heart failure visits, and death at 1 year. With the approval of the FDA, the statistical analysis plan was updated to pre-specify sensitivity analyses to assess the impact of COVID-19 on the trial. For the 72% of patients who completed follow-up prior to the public health emergency declaration in March 2020, a statistically significant 19% reduction in the primary endpoint was reported, driven by a 28% reduction in HFH. However, lifestyle changes during the COVID-19 pandemic such as changes in physical activity, exposure to infections, willingness to seek medical care, and adherence to medications are unmeasured and add imprecision to treatment effect estimates, as do alterations in provider behaviors. Enrollment of NYHA Class II patients was significantly enriched in the first 500 patients, potentially impacting the pre-COVID-19 analysis. The MONITOR-HF trial, an open-label RCT conducted in the Netherlands, showed that hemodynamic monitoring significantly improved quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) and reduced HFH but did not impact mortality at 1 year follow-up. Overall, the beneficial effect of CardioMEMS, if any, appears to be on the hospitalization outcome of the composite. Both urgent heart failure visits and death outcomes had hazard ratios favoring the control group with wide confidence intervals including the null value in pre-COVID-19, during-COVID-19, and overall analyses of the GUIDE-HF trial. The MONITOR-HF trial found improvement in quality of life on the KCCQ for the CardioMEMS group relative to the control, but no significant differences were observed in secondary quality of life and functional status outcomes in the other included trials. While the HFH reduction of 28% found in the pre-COVID-19 analysis is consistent with findings from the CHAMPION trial, it is unclear whether physician knowledge of treatment assignment biases the decision to hospitalize and administer intravenous diuretics. The two included meta-analyses showed a reduction in HFHs with hemodynamic monitoring in heart failure patients but had discordant findings regarding the impact on mortality. One meta-analysis found no pooled difference in mortality between hemodynamic monitoring and control groups; however, a patient-level meta-analysis revealed a significant 25% decrease in mortality associated with hemodynamic monitoring in patients with heart failure with reduced ejection fraction. Given that the intervention is invasive and intended to be used for a highly prevalent condition and, in light of the conflicting evidence of benefit on mortality and functional outcomes, the lack of periprocedural safety data, and unclear impact of COVID-19 on remote monitoring in the GUIDE-HF trial, the net benefit of the CardioMEMS device remains uncertain. Concerns may be clarified by the ongoing open access phase of the GUIDE-HF RCT and the German non-industry-sponsored PASSPORT-HF trial. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have heart failure in outpatient settings who receive hemodynamic monitoring by thoracic bioimpedance, the evidence includes uncontrolled prospective studies and case series. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. There is a lack of RCT evidence evaluating whether the use of these technologies improves health outcomes over standard active management of heart failure patients. The case series have reported physiologic measurement-related outcomes and/or associations between monitoring information and heart failure exacerbations, but do not provide definitive evidence on device efficacy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have heart failure in outpatient settings who receive hemodynamic monitoring with inert gas rebreathing, no studies have been identified on clinical validity or clinical utility. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have heart failure in outpatient settings who receive hemodynamic monitoring of arterial pressure during the Valsalva maneuver, a single study was identified. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. The study assessed the use of left ventricular end-diastolic pressure (LVEDP) monitoring and reported an 85% sensitivity and an 80% specificity to detect LVEDP greater than 15 mm Hg. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information

Not applicable.

Objective

The objective of this evidence review is to determine whether outpatient hemodynamic monitoring improves the net health outcome in individuals with heart failure.

Policy Statements

In the ambulatory care and outpatient setting, cardiac hemodynamic monitoring for the management of heart failure using implantable direct pressure monitoring of the pulmonary artery, thoracic bioimpedance, inert gas rebreathing, and arterial pressure during the Valsalva maneuver is considered investigational

Policy Guidelines

This policy refers only to the use of stand-alone cardiac output measurement devices designed for use in ambulatory care and outpatient settings. The use of cardiac hemodynamic monitors or intrathoracic fluid monitors that are integrated into other implantable cardiac devices, including implantable cardioverter defibrillators, cardiac resynchronization therapy devices, and cardiac pacing devices, is addressed in evidence review 02.002.009

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Chronic Heart Failure

Patients with chronic heart failure are at risk of developing acute decompensated heart failure, often requiring hospital admission. Patients with a history of acute decompensation have the additional risk of future episodes of decompensation and death. Reasons for the transition from a stable, chronic state to an acute, decompensated state include disease progression, as well as acute events such as coronary ischemia and dysrhythmias. While precipitating factors are frequently not identified, the most common preventable cause is noncompliance with medication and dietary regimens.^1,

Management

Strategies for reducing decompensation, and thus the need for hospitalization, are aimed at early identification of patients at risk for imminent decompensation. Programs for early identification of heart failure are characterized by frequent contact with patients to review signs and symptoms with a health care provider, education, and medication adjustments as appropriate. These encounters may occur face-to-face in the office or at home, or via cellular or computed technology.^2,

Precise measurement of cardiac hemodynamics is often employed in the intensive care setting to carefully manage fluid status in acutely decompensated heart failure. Transthoracic echocardiography, transesophageal echocardiography, and Doppler ultrasound are noninvasive methods for monitoring cardiac output on an intermittent basis for the more stable patient but are not addressed herein. A variety of biomarkers and radiologic techniques may be used for dyspnea when the diagnosis of acute decompensated heart failure is uncertain.

The criterion standard for hemodynamic monitoring is pulmonary artery catheters and central venous pressure catheters. However, they are invasive, inaccurate, and inconsistent in predicting fluid responsiveness. Several studies have demonstrated that catheters fail to improve outcomes in critically ill patients and may be associated with harm. To overcome these limitations, multiple techniques and devices have been developed that use complex imaging technology and computer algorithms to estimate fluid responsiveness, volume status, cardiac output and tissue perfusion. Many are intended for use in outpatient settings but can be used in the emergency department, intensive care unit, and operating room. Four methods are reviewed here: implantable pressure monitoring devices, thoracic bioimpedance, inert gas rebreathing, and arterial waveform during the Valsalva maneuver. Use of the last 3 is not widespread because of several limitations including use of proprietary technology making it difficult to confirm their validity and lack of large randomized controlled trials to evaluate treatment decisions guided by these hemodynamic monitors.

Regulatory Status

Noninvasive Left Ventricular End-Diastolic Pressure Measurement Devices

In 2004, the VeriCor^® (CVP Diagnostics), a noninvasive left ventricular end-diastolic pressure measurement device, was cleared for marketing by U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices for the following indication:

"The VeriCor is indicated for use in estimating non-invasively, left ventricular end-diastolic pressure (LVEDP). This estimate, when used along with clinical signs and symptoms and other patient test results, including weights on a daily basis, can aid the clinician in the selection of further diagnostic tests in the process of reaching a diagnosis and formulating a therapeutic plan when abnormalities of intravascular volume are suspected. The device has been clinically validated in males only. Use of the device in females has not been investigated."

FDA product code: DXN.

Thoracic Bioimpedance Devices

Multiple thoracic impedance measurement devices that do not require invasive placement have been cleared for marketing by the FDA through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices used for peripheral blood flow monitoring. Table 1 presents an inexhaustive list of representative devices (FDA product code: DSB).

Table 1. Noninvasive Thoracic Impedance Plethysmography Devices

Also, several manufacturers market thoracic impedance measurement devices integrated into implantable cardiac pacemakers, cardioverter defibrillator devices, and cardiac resynchronization therapy devices. Thoracic bioimpedance devices integrated into implantable cardiac devices are addressed in evidence review 2.02.10.

Inert Gas Rebreathing Devices

In 2006, the Innocor^® (Innovision), an inert gas rebreathing device, was cleared for marketing by the FDA through the 510(k) process. The FDA determined that this device was substantially equivalent to existing inert gas rebreathing devices for use in computing blood flow. FDA product code: BZG.

Implantable Pulmonary Artery Pressure Sensor Devices

In 2014, the CardioMEMS™ Champion Heart Failure Monitoring System (CardioMEMS, now Abbott) was approved for marketing by the FDA through the premarket approval process. This device consists of an implantable pulmonary artery (PA) sensor, which is implanted in the distal PA, a transvenous delivery system, and an electronic sensor that processes signals from the implantable PA sensor and transmits PA pressure measurements to a secure database.^3, The device originally underwent FDA review in 2011, at which point FDA found no reasonable assurance that the monitoring system would be effective, particularly in certain subpopulations, although the FDA agreed this monitoring system was safe for use in the indicated patient population.^4, . In 2022, the CardioMEMS Heart Failure Monitoring System received expanded approval for the treatment of New York Heart Association (NYHA) Class II-III patients who had been hospitalized at least 1 time in the prior year and/or had elevated natriuretic peptides.

Several other devices that monitor cardiac output by measuring pressure changes in the PA or right ventricular outflow tract have been investigated in the research setting but have not received the FDA approval. They include the Chronicle® implantable continuous hemodynamic monitoring device (Medtronic), which includes a sensor implanted in the right ventricular outflow tract, and the ImPressure® device (Remon Medical Technologies), which includes a sensor implanted in the PA.

Note: This evidence review only addresses the use of these technologies in ambulatory care and outpatient settings.

Rationale

This evidence review was created in July 2010 by combining 2 existing evidence reviews and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through  May 3, 2024.

For the first indication, because there is direct evidence from a large randomized controlled trial (RCT), we focus on it and assess the evidence it provides on clinical utility. Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The RCT is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

For indications 2, 3, and 4, we assess the evidence as a medical test. Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1

Implantable Pulmonary Artery Pressure Monitoring

(CardioMEMS Device)

Clinical Context and Therapy Purpose

The purpose of the CardioMEMS system in patients who have heart failure is to provide remote monitoring for early symptoms of heart failure in order to modify therapy and prevent or reduce hospitalization.  Studies on the safety and/or efficacy of the CardioMEMS system consist of 2 RCTs (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA III Heart Failure Patients [CHAMPION], Hemodynamic GUIDEd Management of Heart Failure [GUIDE-HF]) and several nonrandomized studies featuring pre-post, matched cohort comparative, and postmarket surveillance analyses.

The following PICO was used to select literature to inform this review.

Populations

The relevant population(s) of interest is patients with New York Heart Association (NYHA) Class II-IV heart failure who have had a hospitalization in the past year  and/or have elevated natriuretic peptides.

Interventions

Left ventricular end-diastolic pressure (LVEDP) can be approximated by direct pressure measurement of an implantable sensor in the pulmonary artery wall or right ventricular outflow tract. The sensor is implanted via right heart catheterization and transmits pressure readings wirelessly to external monitors. One device, the CardioMEMS Heart Failure Monitoring System, has approval from the U.S. Food and Drug Administration (FDA) for the ambulatory management of heart failure patients. The CardioMEMS device is implanted using a heart catheter system fed through the femoral vein and generally requires patients to have an overnight hospital admission for observation after implantation. Specific target pressure ranges provided to investigators to achieve hemodynamic stability included 10-25 mmHg for mean pulmonary artery pressure, 14-35 mmHg for systolic pressure, and 8-20 mmHg for diastolic pressure. An elevation or decrease in pulmonary artery pressure outside of a patient's individualized baseline was considered to arise from overload or depletion, respectively.

Comparators

The comparator of interest is standard clinical care without hemodynamic testing. Treatment decisions, such as medication adjustments or hospitalization, are made based on changes in clinical signs (eg, body weight, blood pressure, laboratory parameters) and symptoms (eg, dyspnea, fatigue, exercise intolerance) without measurement of pulmonary artery pressure.

Outcomes

The International Consortium for Health Outcomes Measurement has identified 3 domains of outcomes for a standard outcome set for patients with heart failure.^5,

• Survival and disease control (ie, mortality)

• Functioning and disease control (ie, symptom control including dyspnea, fatigue and tiredness, disturbed sleep, and peripheral edema, activities of daily living including health-related quality of life, maximum physical exertion, independence and psychosocial health including depression and anxiety, confidence and self-esteem)

• Burden of care to patient (ie, hospital visits including admissions and appointments, treatment side effects, complications)

The Heart Failure Association of the European Society of Cardiology has published a consensus document on heart failure outcomes in clinical trials.^6, They likewise categorize important outcomes for clinical trials as mortality outcomes (all-cause and cause-specific), morbidity and clinical composites (including hospitalizations, worsening of heart failure, implantable cardioverter device shocks) and symptoms and patient-reported outcomes. The consensus document recommends that hospitalization for heart failure be defined as a hospitalization requiring at least an overnight stay caused by substantive worsening of symptoms and/or signs requiring augmentation of therapy.

Measurements of maximal oxygen consumption during exercise, the 6-minute hall walk test (6MHW), stair climb test, Short Physical Performance Battery or hand-grip strength are functional measures.

Patient-reported outcome measures may include the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire.

Generally, demonstration of outcomes over a 1-year period is meaningful to assess outcomes for the intervention.

Study Selection Criteria

Methodologically credible studies were selected using the following principles.

• Comparative controlled prospective trials were sought, with a preference for RCTs.

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse effects, single-arm studies that capture longer periods of follow-up and/or larger populations will be considered.

• Larger sample size studies and longer duration studies are preferred.

• Studies with duplicative or overlapping populations were excluded.

Post-hoc and/or exploratory subgroup analyses of CardioMEMS trials in patients with reduced ejection fraction,^7,8, preserved ejection fraction,^9, Medicare-eligible patients,^10,chronic obstructive pulmonary disease^11,, and various subtypes of pulmonary hypertension^12, are outside of the scope of this review and are therefore not discussed. Studies reporting physiological measures in the absence of clinical outcomes were also excluded.^13,

Review of Evidence

Iaconelli et al (2023) conducted a systematic review and meta-analysis of RCTs evaluating the use of implantable hemodynamic monitoring devices to guide the management of heart failure.^14, Four trials (COMPASS-HF, REDUCE-HF, CHAMPION, and GUIDE-HF) were determined to be eligible for inclusion with follow-up durations ranging from 6 to 18 months. These trials compared management guided by data from implantable hemodynamic monitoring devices (n=1103; including both the CardioMEMs and Chronicle devices) to standard care (n=1121) in a total of 2,224 heart failure patients. In the pooled analysis, hemodynamic-guided management reduced the risk of total heart failure hospitalizations by 25% (Hazard ratio [HR] 0.75; 95% CI 0.58 to 0.96; p =.03) but did not significantly reduce all-cause mortality (Risk ratio 0.92; 95% CI 0.68 to 1.26; p =.48). Changes in treatment guided by hemodynamic monitoring resulted in small reductions in mean pulmonary artery pressure less than 1 mmHg as a daily average. The COMPASS-HF and REDUCE-HF studies investigated the Chronicle device, which is not FDA-approved and is not otherwise reviewed in this medical policy.

Lindenfeld et al (2024) reported the results of a patient-level meta-analysis of 3 RCTs (GUIDE-HF, CHAMPION, and LAPTOP-HF) evaluating CardioMEMs hemodynamic monitoring for the management of patients with heart failure and a left ventricular ejection fraction ≤40%.^15, The meta-analysis included 1,350 patients with a median follow-up of 12.2 months with a maximum follow-up of 4 years. Patients were randomized to a treatment group receiving hemodynamic-guided management via CardioMEMs (n=667) or a control group receiving standard care (n=683). The pooled analysis demonstrated a significant 36% reduction in heart failure hospitalizations (HR: 0.64; 95% CI: 0.55 to 0.76; p<.0001) and a significant 25% reduction in mortality (HR: 0.75; 95% CI: 0.57 to 0.99; p=.043) in the treatment group compared to the control group. This mortality benefit was observed after the first year of follow-up. The LAPTOP-HF study is only available as an abstract and is not otherwise reviewed in this medical policy.

Randomized Controlled Trials

CHAMPION

Abraham et al (2011, 2016) reported on the results of CHAMPION, a single-blind RCT enrolling patients with NYHA Class III heart failure who have had a hospitalization in the prior year. All enrolled patients were implanted with the CardioMEMS device.^16,17, Patients were randomized to the CardioMEMS group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which investigators were blinded to daily uploaded pressures and managed patients based on clinical signs and symptoms.. An independent clinical endpoints classification (CEC) committee, blinded to the treatment groups, reviewed abstracted clinical data and determined if hospitalization was related to heart failure. It is unclear what criteria were used for adjudication of heart failure hospitalizations.^18,

The randomized phase ended when the last patient enrolled completed at least 6 months of study follow-up (average, 18 months) and was followed in an open-access phase during which investigators had access to pulmonary artery pressure for all patients (former control and treatment group). Trial characteristics and results are summarized in Tables 2 through 4. The trial met its primary efficacy endpoint, with a statistically significant 28% relative reduction in the rate of heart failure-related hospitalizations (HFH) at 6 months. This outcome was accompanied by a significant improvement in MLHFQ scores at 6 and 12 months. No significant reduction in mortality was observed at 6 months or at the conclusion of the randomized phase. However, members of the FDA advisory committee in 2011 were unable to distinguish the effect of the device on HFH from the effect of nurse communications in cases where the investigator did not document a medication change in response to an abnormal pulmonary artery pressure elevation. Therefore, the FDA denied the initial approval of CardioMEMS and requested additional clarification from the manufacturer.^3, Subsequently, the FDA held a second advisory committee meeting in 2013 to review additional data (including open-access phase) and address previous concerns related to the impact of nurse communication on the CHAMPION trial.^19,20, Post-hoc analyses to address the impact of nurse interventions on HFH conducted by the sponsor were judged to have methodologic limitations by the FDA.^3, However, the FDA stated that longitudinal analyses, such as those demonstrating a significant decrease in HFH when former control patients entered the treatment arm of the open-access phase, were the most useful regarding support for device effectiveness. It is important to acknowledge that all such analyses were conducted with the intent to test the robustness of potentially biased RCT results; therefore, results from these analyses should be evaluated to assess consistency and ­­­­­not as an independent source of evidence to support efficacy. Additional trial aspects limit the interpretation of these analyses; notably, subject dropouts were not random, and patient risk profiles could have changed from the randomized phase to the open-access phase. In the open-access phase, 93 (34%) of 270 subjects in the treatment group and 110 (39%) of 280 subjects in the control group remained in the analysis.

While the CHAMPION trial failed to demonstrate a treatment effect in women, the overall reduction in HFH subsequently observed in the CardioMEMS post-approval study (see Tables 7 and 8) was also observed in the subgroup analysis of women, which comprised 37.7% of the study population.^21,22,

GUIDE-HF

Lindenfeld et al (2021) reported on the results of the Hemodynamic GUIDEd Management of Heart Failure trial (GUIDE-HF), a single-blind RCT in which all patients were implanted with the CardioMEMS device.^23, As in the CHAMPION trial, patients were randomized to control and treatment groups in which investigators were blinded or unblinded, respectively, to pulmonary artery pressures uploaded daily by all patients. The GUIDE-HF trial expanded enrollment to patients with NYHA Class II-IV heart failure with a hospitalization in the prior year and/or elevated natriuretic peptides. Patient management was composed of 2 phases: (1) an optimization phase through 3 months post-implantation and (2) a maintenance phase. The optimization phase required clinicians to monitor and manage patients more closely to optimize pulmonary artery pressures to an individualized target range, while the maintenance phase focused on maintaining optimal pulmonary artery pressures. Generally, a 3 to 5 mm Hg persistent pressure change over 2 to 3 days or a change of 5 mm Hg in a single day were recommended as actionable deviations. Blinded trial personnel were instructed to contact subjects with scripted language provided by unblinded study coordinators at least once every 2 weeks during the optimization phase and at least monthly during the maintenance phase. Efforts were made to balance the frequency of site-initiated communications.

Trial characteristics and results are summarized in Tables 2 through 4. The GUIDE-HF trial failed to meet its overall primary efficacy endpoint, finding a statistically insignificant 12% reduction in the composite of HFH (>24 h due to acute decompensation and requiring administration of intravenous diuretics), urgent heart failure visits (ie, unscheduled or unplanned admission to the emergency department, hospital outpatient observation visit, or hospital inpatient visit [<24 h] due to acute decompensation and requiring administration of intravenous diuretics), and all-cause mortality at 12 months post-implantation. An independent CEC committee adjudicated all endpoints contributing to the primary outcome to confirm that they were heart failure-related. No significant improvements in individual components of the primary outcome or secondary efficacy endpoints were observed in GUIDE-HF. Subgroup analyses for the primary endpoint found a reduced treatment effect in patients with NYHA Class IV heart failure and men. The more favorable treatment effect in women observed in GUIDE-HF is inconsistent with results from the CHAMPION trial which found limited benefit. Overall, fewer patients were receiving primary classes of guideline-directed medical therapy at 12 months in both treatment and control groups. A significantly higher reduction in mean pulmonary artery pressure was observed in the treatment group; however, it is unclear whether the proportion of patients meeting target pressure ranges improved and whether absolute reductions were clinically meaningful.

With approval from the FDA in August 2020, the statistical analysis plan was updated to include sensitivity analyses with a 15% interaction significance level to evaluate the possible impact of the COVID-19 pandemic. Results of overall, pre-COVID-19, and during-COVID-19 analyses are summarized in Table 3. All patients were enrolled for at least 3 months and 71.7% of follow up occurred before the US national emergency declaration date of March 13, 2020. The CEC committee determined that there were 7 events related or possibly related to COVID-19; all occurring in the control group. Planned sensitivity analyses based on the timing of the COVID-19 pandemic included evaluation of primary endpoint events observed for subjects completing study participation prior to the pandemic and for subject follow-up occurring prior to the pandemic. The pre-COVID-19 impact analysis based on subject follow-up suggested an effect of COVID-19 on the primary endpoint (p=.11). A significant 19% reduction (p=.049) in the primary endpoint was found, driven by a 28% reduction in HFH (p=.0072). No significant improvements in heart failure visits, mortality, or secondary efficacy outcomes were observed. Additional analysis of patient data obtained during the COVID-19 pandemic as subsequently reported by Zile et al (2022)^24, failed to find a significant reduction in the composite outcome and its individual components. Study authors noted that this was driven by an unexpected reduction in the primary event rate in the control group, potentially due to patient-dependent factors.

Study relevance, design, and conduct limitations are summarized in Tables 5 and 6. Lifestyle changes during the pandemic such as changes in physical activity, exposure to infections, willingness to seek medical care, and adherence to medications are unmeasured and add imprecision to treatment effect estimates. During COVID-19, the monthly rate of medication changes fell by 19.2% in the treatment group and 10.7% in the control group. This was accompanied by a deintensification of medication management (ie, decreased ratio of dosage increases to decreases) by 8.8% and 17.4% in the treatment and control groups, respectively. The number of site-initiated (blinded) and overall contacts was similar pre- and during-COVID-19 after exclusion of contacts occurring in the initial 90-day optimization phase. The final 500 trial subjects enrolled had a significantly higher proportion of NYHA Class III-IV heart failure as enrollment of subjects with NYHA Class II heart failure was limited to 300 patients. Reductions in mean pulmonary artery pressure were not significantly different between groups during COVID-19 and it is unclear what proportion of medication changes were concordant with deviations in hemodynamic data over the course of the trial.

MONITOR-HF

Brugts et al (2023) reported the results of MONITOR-HF, an open-label RCT conducted in 25 centers in the Netherlands.[Brugts JJ, Radhoe SP, Clephas PRD, et al. Remote h.... 394): 2113-2123. PMID 37220768] Eligible patients had NYHA class III chronic heart failure, a previous heart failure hospitalization, and had been treated with optimal or maximally tolerated treatment according to the European Society of Cardiology guidelines. Patients were randomly assigned (1:1) to either hemodynamic monitoring using CardioMEMS or standard of care. All patients were scheduled for follow-up at 3 months, 6 months, and every 6 months thereafter, up to 48 months. In the control group, patients were managed with guideline-directed medical therapy and diuretics based on signs, symptoms, laboratory measurements, and echocardiography without hemodynamic information. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. Trial characteristics and results are summarized in Tables 2 through 4. The MONITOR-HF study achieved its primary efficacy endpoint, demonstrating a statistically significant change in the mean KCCQ overall summary score at 12 months, favoring the CardioMEMs group with a mean difference of 7.05 points (95% CI: 2.77 to 11.33; p=.013) compared to the control group. Secondary outcomes included a responder analysis that revealed the CardioMEMS group had a significantly higher proportion of patients achieving a ≥ 5-point improvement in KCCQ score at 12 months compared to the standard of care group (47.7% vs. 38.1%, p = 0.046). Participants in the CardioMEMS group also experienced a lower rate of total heart failure hospitalizations or urgent visits requiring IV diuresis, with 117 events per patient-year compared to 212 in the standard of care group (HR 0.56; 95% CI 0.38 to 0.84l; p=.0053). Additionally, the CardioMEMS group showed a significant reduction in median NT-proBNP levels at 12 months (-669 pg/mL, p = 0.013) and a significant improvement in mean 6-minute walk test distance (+29.3 m, p = 0.033), while the control group did not demonstrate significant changes in these parameters. Freedom from sensor failure in the CardioMEMS group was 98.8%. The trial included a sensitivity analysis to assess the potential impact of the COVID-19 pandemic on the results. The analysis revealed no significant interaction between the treatment effects and the COVID-19 pandemic. Study relevance, design, and conduct limitations are summarized in Tables 5 and 6. Limitations of the MONITOR-HF study included the lack of blinding, the absence of sham control, and the treatment arm having a two-month lead-in optimization phase which was not present in the control group.

Table 2. Summary of Key Randomized Controlled Trial Characteristics

CHAMPION: CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA III Heart Failure Patients trial; ESC: European Society of Cardiology; GUIDE-HF: Hemodynamic GUIDEd Management of Heart Failure trial; HF: heart failure; HFH: heart failure hospitalization; NR: not reported; NYHA: New York Heart Association; PAP: pulmonary artery pressure

Table 3. Summary of Key Randomized Controlled Trial Results: Main Safety and Efficacy Outcomes

CHAMPION: CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA III Heart Failure Patients trial; CI: confidence interval; GUIDE-HF: Hemodynamic GUIDEd Management of Heart Failure trial; HF: heart failure; HFH: heart failure hospitalization; HR: hazard ratio; NA: not applicable; NR: not reported; a Primary efficacy outcome in CHAMPION trial.b Primary efficacy outcome in GUIDE-HF trial.

Table 4. Summary of Key Randomized Controlled Trial Results: Secondary Outcomes

6MHW: 6 minute Hall Walk; AUC: area under the curve; CHAMPION: CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA III Heart Failure Patients trial; EQ-5D-5L VAS: EuroQOL 5-dimension 5-level Visual Analog Scale questionnaire; GUIDE-HF: Hemodynamic GUIDEd Management of Heart Failure trial; kCCQ-12: Kansas MLHFQ: Minnesota Living with Heart Failure Questionnaire; NA: not applicable; NR: not reported; SD: standard deviation.a Higher scores (range, 0-105) indicate more significant impairment in health-related quality of life.b Higher scores (range, 0-100) indicate better health status. c Higher scores (range, 0-100) indicate better health status.d Increased distances indicate improved functional capacity.

Tables 5 and 6 display notable limitations identified in each study.

Table 5. Study Relevance Limitations

CHAMPION: CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA III Heart Failure Patients trial; GUIDE-HF: Hemodynamic GUIDEd Management of Heart Failure trial.The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not established and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 6. Study Design and Conduct Limitations

CHAMPION: CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA III Heart Failure Patients trial; GUIDE-HF: Hemodynamic GUIDEd Management of Heart Failure trial; HF: heart failure; NYHA: New York Heart Association. The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated; 5. Other.

Nonrandomized Studies

As previously described in the selection criteria, studies will be included here to assess long-term outcomes and adverse effects if they capture longer periods of follow-up and/or larger populations than the RCTs. Nonrandomized studies have featured pre-post, retrospective matched cohort, and post-market surveillance analyses. Key nonrandomized study characteristics and results are summarized in Tables 7 and 8. Nonrandomized study relevance, design, and conduct limitations are summarized in Tables 9 and 10.

Kishino et al (2022) analyzed the Nationwide Readmissions Database (NRD) between 2014 and 2019 for patients with CardioMEMS implantation.^26, CardioMEMS patients (n=1839) and their readmissions were compared to a matched cohort of patients with heart failure without CardioMEMS implantation (n=1924). Readmission rates at 30 days (17.35 vs. 21.5%; p=.002), 90 days (29.6% vs. 36.5%; p=.002), and 180 days (39.6% vs. 46.6%; p=.009) were lower in the CardioMEMS group. Based on multivariable regression analysis, only use of the CardioMEMS device was associated with a significantly lower risk of readmission at 30 days (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.63 to 0.89; p=.001), 90 days (HR, 0.73; 95% CI, 0.63 to 0.86; p<.001) and 180 days (HR, 0.80; 95% CI, 0.71 to 0.91; p=.001). However, in-hospital mortality at 30 days was significantly higher in the CardioMEMS group both before (6.9% vs. 2.8%; p<.001) and after propensity score matching (7% vs. 3.6%; p=.002). Use of the CardioMEMS device was also associated with higher rates of acute kidney injury (43.8% vs. 34.7%; p<.001), acute kidney injury requiring hemodialysis (3.5% vs. 1.8%; p=.019), and transfusions (9.8% vs. 3.4%; p<.001).

Cowie et al (2021) published 1-year outcomes from the prospective, international, multicenter, open-label CardioMEMS HF System for Post-Market Study (COAST).^27, The study was designed to evaluate the safety, feasibility, and effectiveness of hemodynamic-guided heart failure management in patients with NYHA Class III heart failure in the UK, Europe, and Australia. The current report focuses on initial results from COAST-UK, which evaluated the first 100 patients who completed all follow-up in the UK before the COVID-19 pandemic emergency declaration date. The primary efficacy outcome was the change in the annualized HFH rate during the 12 months prior to implantation compared with 12 months after implantation. All clinical events were adjudicated by investigators responsible for the treatment. There were 165 HFH events (1.52 events/patient-year) before implant and 27 HFH events (0.27 events/patient-year) after implant, resulting in a significant 82% risk reduction (HR, 0.178; 95% confidence interval CI, 0.12 to 0.28; p<.0001). No significant improvements in EQ-5D-5L scores were observed at 6- or 12-month time points. Over 12 months, functional class improvements were noted for 41 patients reclassified as NYHA Class II and 3 patients reclassified as Class I. The primary safety endpoints of freedom from device- and system-related complications and freedom from pressure sensor failures at 2 years occurred in 100% and 99% of patients, respectively, exceeding pre-specified performance goals of 80% and 90%, respectively.

Shavelle et al (2020) reported 1-year outcomes from the open-label, observational, single-arm, post-approval study of CardioMEMS in 1200 patients (37.7% female) across 104 centers in the U.S. with NYHA Class III heart failure and a HFH event in the prior year.^21, The primary efficacy outcome was the difference between rates of adjudicated HFH 1 year after compared to 1 year prior to device implantation. The 12-month visit was completed in 875 patients (72.9%). Prior to 1 year, 76 patients (6.3%) withdrew from the study and 186 patients (15.5%) died. The HFH rate was significantly lower at 1 year post-implantation (0.54 vs. 1.25 events/patient-year; HR, 0.43; 95% CI, 0.39 to 0.47; p<.0001). The rate decrease remained significant regardless of the number of pre-enrollment HFH events, with a trend towards a more significant benefit in a small subgroup of patients (n=21) with ≥5 pre-enrollment HFH events. The rate of all-cause hospitalization (ACH) was also significantly lower (1.67 vs. 2.28 events/patient-year; HR, 0.73; 95% CI, 0.68 to 0.78; p<.0001). During the study, 94.1% of patients had a medication change, with an average of 1.6 medication changes per month. Medication changes related to an increase or decrease in pulmonary artery pressure were implemented in 81.8% and 55.8% of patients, respectively. At 1 year, freedom from device- or system-related complications was 99.6% (5 events) and freedom from pressure sensor failure was 99.9% (1 event). The nature of these events and the frequency of procedure-related adverse events were not reported. Heywood et al published 2-year outcomes from the U.S. post-approval study in 2023.^28, Two-year follow-up was completed by 710 patients (59.2%). Both HFH and ACH rates further decreased at 2 years to 0.37 events/patient-year (HR, 0.69; 95% CI, 0.58 to 0.82; p<.0001) and 1.42 events/patient-year (HR, 0.85; 95% CI, 0.77 to 0.94; p=.0014), respectively. During 2 year follow-up, 59.4% of all participants experienced freedom from HFH. Of 487 patients who were hospitalized, 53.6% were only hospitalized once. The rate of medication changes declined from 1.3 per subject in the first 90 days compared to 1.3 at years 1 and 2. Compared to baseline, the change in mean pulmonary artery pressure was -2.4 mm Hg at 1 year and -2.6 mm Hg at 2 years. Therefore, despite the decreasing frequency of interventions over time, the reduction of mean pulmonary artery pressures was largely sustained. Freedom from device- or system-related complications was 99.6% at 2 years, exceeding the 80% predefined performance goal for the primary safety endpoint. Freedom from sensor failure was 99.9%, exceeding the 90% predefined performance goal. The mortality rate through 2 years was 29%.

Angermann et al (2020) published results from the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF).^29, This was an industry-sponsored, prospective, observational, non-randomized study designed to assess the safety and feasibility of the CardioMEMS heart failure system over a 12-month follow up in 31 centers across Germany, the Netherlands, and Ireland. A total of 239 patients (22% female) with NYHA class III heart failure and ≥1 HFH in the prior year were enrolled for remote pulmonary artery pressure-guided heart failure management. Co-primary outcome measures, 1-year rates of freedom from device- or system-related complications and sensor failure, were 98.3% (95% CI, 95.8 to 100) and 99.6% (95% CI, 97.6 to 100), respectively. Twenty-one serious adverse events (8.9%) were reported during 236 implant attempts, of which 4 were categorized as device- or system-related and 21 as procedure-related. Three procedure-related cardiac deaths were reported. The overall 12-month mortality rate was 13.8%, with no device- or system-related deaths. The secondary outcome measures included HFH rate at 12 months compared to the prior year before implantation and health-related quality of life. The HFH rate decreased 62% (0.60 vs. 1.55 events/patient year; HR, 0.38; 95% CI, 0.31 to 0.48; p<.0001). These reductions were consistent across subgroups defined by sex, age, heart failure etiology, device use, ejection fraction, baseline pulmonary artery pressure, and various comorbidities. Patient-reported health-related quality of life outcomes were assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), 9-Item Patient Health Questionnaire (PHQ-9), and the EQ-5D-5L. All measures significantly improved at 6 months and were sustained through 12 months. Cumulative medication changes and the average rate of monthly per-patient medication changes were highest in months 0 to 3 postimplant.

Abraham et al (2019) published a retrospective matched cohort study of Medicare beneficiaries who received the CardioMEMS device between 2014 and 2016.^30, Patients were matched to 1087 controls by demographics, history and timing of HFH, and number of ACH. Propensity scoring based on arrhythmia, hypertension, diabetes, pulmonary disease, and renal disease was used for additional matching. Follow-up was censored at death, ventricular assist device implant, or heart transplant. At 12 months postimplantation, 616 and 784 HFH events occurred in the treatment and control cohorts, respectively. Study characteristics and results are summarized in Tables 7 and 8. The rate of HFH was lower in the treatment cohort at 12 months (HR, 0.76; 95% CI, 0.65 to 0.89; p<.001). Percentage of days lost to HFH (HR, 0.73; 95% CI, 0.64 to 0.84; p<.001) and ACH or death (HR, 0.77; 95% CI, 0.68 to 0.88; p<.001) were both significantly lower in the treatment group. The percentage of days lost owing to HFH or death was reduced in the treatment cohort (relative risk [RR], 0.73; 95% CI, 0.63 to 0.83).

Desai et al (2017) published a retrospective cohort study of Medicare administrative claims data for individuals who received the CardioMEMS device following the FDA approval.^31, Of 1935 Medicare enrollees who underwent implantation of the device, 1114 were continuously enrolled and had evaluable data for at least 6 months before, and following, implantation. A subset of 480 enrollees had complete data for 12 months before and after implantation. The cumulative incidence of HFH events was significantly lower in the postimplantation period than in the preimplantation period at both 6- and 12-month follow-ups.

Postmarketing Safety

Lin et al (2022) analyzed the FDA Manufacturer and User Facility Device Experience (MAUDE) database for adverse events filed for the CardioMEMS device from May 2014 to November 2020.^32, A conservative approach was used, with reports with multiple events counted once for the most severe event. A total of 2861 reports were filed in the reporting period, of which 2858 (99.9%) were categorized as mandatory reports by the manufacturer or user facility. Per 6-month period between May 2014 and May 2017, the mean number of reports was 41, increasing to 356 in the second half of 2017. The majority of reports were for inaccurate measurements requiring replacement of the external CardioMEMS unit (n=1109; 38.8%), repeat noninvasive testing (n=314; 11.0%), repeat right heart catheterization (n=677; 23.7%), or surgery (n=23; 0.8%). Nonfatal complications included hemoptysis (n=70; 2.4%), heart failure exacerbation (n=43; 1.5%), and significant bleeding at the site of catheterization (n=24; 0.8%). Patient death or transition to end-of-life care was the terminal event in 167 (5.8%) reports. The authors suggest that the safety of CarioMEMS be considered in the context of its lack of a mortality benefit in multiple RCTs, particularly in light of approved expanded use in individuals with NYHA class II heart failure.

Vaduganathan (2017) analyzed mandatory and voluntary reports of device-related malfunctions reported to the FDA to identify CardioMEMS system-related adverse events within the first 3 years of the FDA approval.^33, From among the more than 5500 CardioMEMS implants in the first 3 years, there were 155 adverse event reports covering 177 distinct adverse events for a rate of 2.8%. There were 28 reports of pulmonary artery injury/hemoptysis (0.5%) that included 14 intensive care unit stays, 7 intubations, and 6 deaths. Sensor failure, malfunction, or migration occurred in 46 cases, of which 35 required recalibrations. Compared with a reported 2.8% event rate, the serious adverse event rate in the CHAMPION trial was 2.6% with 575 implant attempts, including 1 case of pulmonary artery injury and 2 deaths.

Table 7. Summary of Key Nonrandomized Study Characteristics

AHRQ: Agency for Healthcare Research and Quality; FDA: U.S. Food and Drug Administration; HF: heart failure; HFH: heart failure-related hospitalization; MAUDE:Manufacturer and User Facility Device Experience; NA: not applicable; NYHA: New York Heart Association,

Table 8. Summary of Key Nonrandomized Study Results

AE: adverse event; CI: confidence interval; DSRC: device- or system-related complications, HFH: heart failure hospitalization; HR: hazard ratio; MAUDE:Manufacturer and User Facility Device Experience; NR: not reported; SAE: serious adverse event.a The primary efficacy analysis consisted of all 234 patients implanted with the CardioMEMS device. b Results at 12-month follow-up as completed by 180 patients. 

Table 9. Nonrandomized Study Relevance Limitations

NYHA: New York Heart Association.The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not established and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 10. Nonrandomized Study Design and Conduct Limitations

HFH: heart failure hospitalization; RCT: randomized controlled trial.The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated; 5. Other

Section Summary: Implantable Pulmonary Artery Pressure Monitoring (CardioMEMS Device)

The pivotal CHAMPION RCT reported a statistically significant 28% decrease in HFH in patients implanted with CardioMEMS device compared with usual care at 6 months. However, trial results were potentially biased in favor of the treatment group due to the use of additional nurse communication to enhance protocol compliance with the device. The subsequent GUIDE-HF RCT failed to meet its primary efficacy endpoint, the composite of HFH, urgent heart failure visits, and death at 1 year. With the approval of the FDA, the statistical analysis plan was updated to pre-specify sensitivity analyses to assess the impact of COVID-19 on the trial. For the 72% of patients who completed follow-up prior to the public health emergency declaration in March 2020, a statistically significant 19% reduction in the primary endpoint was reported, driven by a 28% reduction in HFH. The MONITOR-HF trial, an open-label RCT conducted in the Netherlands, showed that hemodynamic monitoring significantly improved quality of life and reduced HFH but did not impact mortality. Nonrandomized studies have also consistently reported significant reductions in HFH, but are limited by the use of historical controls, within-group comparisons, and retrospective claims data. The impact of COVID-19 on the GUIDE-HF trial met the pre-specified 15% interaction significance level. However, lifestyle changes during the COVID-19 pandemic such as changes in physical activity, exposure to infections, willingness to seek medical care, and adherence to medications are unmeasured and add imprecision to treatment effect estimates. Provider behaviors may have also been altered, partly evidenced by decreased medication changes and deintensification of medical management during COVID-19. Enrollment of NYHA Class II patients was significantly enriched in the first 500 patients enrolled, potentially impacting the pre-COVID-19 analysis.

Overall, the beneficial effect of CardioMEMS, if any, appears to be on the hospitalization outcome of the composite. Both urgent heart failure visits and death outcomes had HRs favoring the control group with wide CIs including the null value in pre-COVID-19, during-COVID-19, and overall analyses of the GUIDE-HF trial. The MONITOR-HF trial found improvement in quality of life on the Kansas City Cardiomyopathy Questionnaire for the CardioMEMS group relative to control, but no significant differences were observed in secondary quality of life and functional status outcomes in the other included trials. While an HFH reduction of 28% found in the pre-COVID-19 analysis is consistent with findings from the CHAMPION trial, it is unclear whether physician knowledge of treatment assignment biases the decision to hospitalize and administer intravenous diuretics. Two meta-analyses were included, which found a significant reduction in HFHs but conflicting findings on mortality, with one finding no difference between hemodynamic monitoring and control with another patient-level meta-analysis which demonstrated a significant 25% reduction in mortality with hemodynamic monitoring in patients with heart failure with reduced ejection fraction. Given the discordant findings regarding mortality benefits in the meta-analyses as well as mixed findings of the benefits to functional outcomes, lack of procedural safety data, and unclear impact of COVID-19 on remote monitoring in the GUIDE-HF trial, the net benefit of the CardioMEMS device remains uncertain. Concerns may be clarified by the ongoing open access phase of the GUIDE-HF RCT and the German non-industry-sponsored PASSPORT-HF trial.

Section Summary: Implantable Pulmonary Artery Pressure Monitoring (CardioMEMS Device)

The pivotal CHAMPION RCT reported a statistically significant 28% decrease in HFH in patients implanted with CardioMEMS device compared with usual care at 6 months. However, trial results were potentially biased in favor of the treatment group due to the use of additional nurse communication to enhance protocol compliance with the device. The subsequent GUIDE-HF RCT failed to meet its primary efficacy endpoint, the composite of HFH, urgent heart failure visits, and death at 1 year. With the approval of the FDA, the statistical analysis plan was updated to pre-specify sensitivity analyses to assess the impact of COVID-19 on the trial. For the 72% of patients who completed follow-up prior to the public health emergency declaration in March 2020, a statistically significant 19% reduction in the primary endpoint was reported, driven by a 28% reduction in HFH. Nonrandomized studies have also consistently reported significant reductions in HFH, but are limited by the use of historical controls, within-group comparisons, and retrospective claims data. The impact of COVID-19 on the GUIDE-HF trial met the pre-specified 15% interaction significance level. However, lifestyle changes during the COVID-19 pandemic such as changes in physical activity, exposure to infections, willingness to seek medical care, and adherence to medications are unmeasured and add imprecision to treatment effect estimates. Provider behaviors may have also been altered, partly evidenced by decreased medication changes and deintensification of medical management during COVID-19. Enrollment of NYHA Class II patients was significantly enriched in the first 500 patients enrolled, potentially impacting the pre-COVID-19 analysis.

Overall, the beneficial effect of CardioMEMS, if any, appears to be on the hospitalization outcome of the composite. Both urgent heart failure visits and death outcomes had HRs favoring the control group with wide CIs including the null value in pre-COVID-19, during-COVID-19, and overall analyses of the GUIDE-HF trial. No significant differences were observed in secondary quality of life and functional status outcomes. While a HFH reduction of 28% found in the pre-COVID-19 analysis is consistent with findings from the CHAMPION trial, it is unclear whether physician knowledge of treatment assignment biases the decision to hospitalize and administer intravenous diuretics. In light of the absence of a demonstrated benefit on mortality and functional outcomes, lack of procedural safety data, and unclear impact of COVID-19 on remote monitoring in the GUIDE-HF trial, the net benefit of the CardioMEMS device remains uncertain. Concerns may be clarified by the ongoing open access phase of the GUIDE-HF RCT and the German non-industry-sponsored PASSPORT-HF trial.

For individuals with New York Heart Association (NYHA) class II-IV heart failure in outpatient settings who have had a hospitalization in the past year and/or have elevated natriuretic peptides who receive hemodynamic monitoring with an implantable pulmonary artery pressure sensor device, the evidence includes 2 meta-analyses, randomized controlled trials (RCTs), and nonrandomized studies. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. One implantable pressure monitor, the CardioMEMS device, has U.S. Food and drug Administration (FDA) approval. The pivotal CHAMPION RCT reported a statistically significant 28% decrease in heart failure hospitalization (HFH) in patients implanted with the CardioMEMS device compared with usual care. However, trial results were potentially biased in favor of the treatment group due to the use of additional nurse communication to enhance protocol compliance with the device. The manufacturer conducted multiple analyses to address potential bias from the nurse interventions. Results were reviewed favorably by the FDA. While these analyses demonstrated the consistency of benefit of the CardioMEMS device, all such analyses have methodologic limitations. Early safety data have been suggestive of a higher rate of procedural complications, particularly related to pulmonary artery injury. While the U.S. CardioMEMS post-approval study and CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) study reported a significant decrease in HFH with few device- or system-related complications at 1 year, the impact of nursing interventions remains unclear. The subsequent GUIDE-HF RCT failed to meet its primary efficacy endpoint, the composite of HFH, urgent heart failure visits, and death at 1 year. With the approval of the FDA, the statistical analysis plan was updated to pre-specify sensitivity analyses to assess the impact of COVID-19 on the trial. For the 72% of patients who completed follow-up prior to the public health emergency declaration in March 2020, a statistically significant 19% reduction in the primary endpoint was reported, driven by a 28% reduction in HFH. However, lifestyle changes during the COVID-19 pandemic such as changes in physical activity, exposure to infections, willingness to seek medical care, and adherence to medications are unmeasured and add imprecision to treatment effect estimates, as do alterations in provider behaviors. Enrollment of NYHA Class II patients was significantly enriched in the first 500 patients, potentially impacting the pre-COVID-19 analysis. The MONITOR-HF trial, an open-label RCT conducted in the Netherlands, showed that hemodynamic monitoring significantly improved quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) and reduced HFH but did not impact mortality at 1 year follow-up. Overall, the beneficial effect of CardioMEMS, if any, appears to be on the hospitalization outcome of the composite. Both urgent heart failure visits and death outcomes had hazard ratios favoring the control group with wide confidence intervals including the null value in pre-COVID-19, during-COVID-19, and overall analyses of the GUIDE-HF trial. The MONITOR-HF trial found improvement in quality of life on the KCCQ for the CardioMEMS group relative to the control, but no significant differences were observed in secondary quality of life and functional status outcomes in the other included trials. While the HFH reduction of 28% found in the pre-COVID-19 analysis is consistent with findings from the CHAMPION trial, it is unclear whether physician knowledge of treatment assignment biases the decision to hospitalize and administer intravenous diuretics. The two included meta-analyses showed a reduction in HFHs with hemodynamic monitoring in heart failure patients but had discordant findings regarding the impact on mortality. One meta-analysis found no pooled difference in mortality between hemodynamic monitoring and control groups; however, a patient-level meta-analysis revealed a significant 25% decrease in mortality associated with hemodynamic monitoring in patients with heart failure with reduced ejection fraction. Given that the intervention is invasive and intended to be used for a highly prevalent condition and, in light of the conflicting evidence of benefit on mortality and functional outcomes, the lack of periprocedural safety data, and unclear impact of COVID-19 on remote monitoring in the GUIDE-HF trial, the net benefit of the CardioMEMS device remains uncertain. Concerns may be clarified by the ongoing open access phase of the GUIDE-HF RCT and the German non-industry-sponsored PASSPORT-HF trial. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Population reference No. 2

Noninvasive Thoracic Bioimpedance/Impedance Cardiography

Clinical Context and Test Purpose

The purpose of thoracic bioimpedance in patients who have heart failure in an outpatient setting is (1) to guide volume management, (2) to identify physiologic changes that precede clinical symptoms and thus allow preventive interventions, and (3) to prevent hospitalizations.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is patients with chronic heart failure who are at risk of developing acute decompensated heart failure (ADHF).

Interventions

The test being considered is thoracic bioimpedance.

Bioimpedance is defined as the electrical resistance of current flow through tissue. For example, when small electrical signals are transmitted through the thorax, the current travels along the blood-filled aorta, which is the most conductive area. Changes in bioimpedance, measured during each beat of the heart, are inversely related to pulsatile changes in volume and velocity of blood in the aorta. Cardiac output is the product of stroke volume by heart rate and, thus, can be calculated from bioimpedance. Cardiac output is generally reduced in patients with systolic heart failure. Acute decompensation is characterized by worsening of cardiac output from the patient's baseline status. The technique is alternatively known as impedance cardiography.

Comparators

The comparator of interest is standard clinical care without testing. Decisions on guiding volume management are being made based on signs and symptoms.

Outcomes

The general outcomes of interest are the prevention of decompensation episodes, reductions in hospitalization and mortality, and improvements in quality of life.

Generally, demonstration of outcomes over a 1-year period is meaningful for interventions.

Study Selection Criteria

Methodologically credible studies were selected using the following principles.

• Comparative controlled prospective trials were sought, with a preference for RCTs.

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse effects, single-arm studies that capture longer periods of follow-up and/or larger populations will be considered.

• Larger sample size studies and longer duration studies are preferred.

• Studies with duplicative or overlapping populations were excluded.

The AMULET RCT (NCT03476590) comparing standard care to outpatient telemedicine based on nurse-led non-invasive assessments was excluded as the impact of impedence cardiography on outcomes beyond the benefits of frequent nursing surveillance cannot be isolated and it is unclear to what extent impedence cardiography was utilized in the standard care setting.^31,

Review of Evidence

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Several studies were excluded from the evaluation of the clinical validity of thoracic bioimpedance testing because they did not include information needed to assess clinical validity.^35,36,37,

Packer et al (2006) reported on the use of impedance cardiography measured by BioZ impedance cardiography monitor to predict decompensation in patients with chronic heart failure.^38, In this study, 212 stable patients with heart failure and a recent episode of decompensation underwent serial evaluation and blinded impedance cardiography testing every 2 weeks for 26 weeks and were followed for the occurrence of death or worsening heart failure requiring hospitalization or emergent care. Results are summarized in Table 11. A composite score of 3 impedance cardiography parameters was a predictor of an event during the next 14 days (p<.001).

Table 11. Clinical Validity of 3-Level Risk Score for BioZ Impedance Cardiography Monitor

CI: confidence interval; ED: emergency department; HF: heart failure.

Section Summary: Clinically Valid

The clinical validity of using thoracic bioimpedance for patients with chronic heart failure who are at risk of developing ADHF has not been established. Association studies are insufficient evidence to determine whether thoracic bioimpedance can improve outcomes in patients with chronic heart failure who are at risk of developing ADHF. There are no studies reporting the clinical validity regarding sensitivity, specificity, or predictive value.

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, more effective therapy, avoid unnecessary therapy, or avoid unnecessary testing.

Direct Evidence

Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs.

Amir et al (2017) reported on the results of a prospective study in which 59 patients recently hospitalized for heart failure were selected for remote dielectric sensing (ReDS)-guided treatment for 90 days.^39, The number of heart failure hospitalizations during 90-day ReDS-guided therapy was compared with hospitalizations in the preceding 90 days before enrollment and the 90 days following discontinuation of ReDS monitoring. During treatment, patients were equipped with the ReDS wearable vest, which was worn once a day at home to measure lung fluid content. Study characteristics and results are summarized in Tables 12 and 13. The rate of heart failure hospitalizations was lower during the ReDS-guided follow-up compared with pre- and post-treatment periods. Interpretation of results is uncertain due to the lack of concurrent control and randomization, short-term follow-up, large CIs, and lack of clarity about lost-to-follow-up during the post-ReDS period. An RCT comparing ReDS monitoring with the standard of care (SMILE; NCT02448342) was initiated but terminated before its completion.

Table 12. Summary of Key Nonrandomized Study Characteristics

FU: follow-up; LVEF: left ventricular ejection fraction; ReDS: remote dielectric sensing; SD: standard deviation.

Table 13. Summary of Key Nonrandomized Study Results

HFH: heart failure-related hospitalizations. a Treatment versus pretreatment period; b Treatment versus posttreatment period.

Chain of Evidence

Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility. Because the clinical validity of using thoracic bioimpedance has not been proved, a chain of evidence to support its clinical utility cannot be constructed.

Section Summary: Clinical Utility

The clinical utility of using thoracic bioimpedance for patients with chronic heart failure who are at risk of developing ADHF has not been established. One prospective longitudinal study reported that ReDS-guided management reduced heart failure readmissions in ADHF patients recently discharged from the hospital. However, interpretation of results is uncertain due to the lack of concurrent controls and randomization, short-term follow-up, large CIs, and lack of clarity about lost-to-follow-up during the post-ReDS monitoring period. An RCT comparing ReDS monitoring with the standard of care was initiated but terminated before its completion.

For individuals who have heart failure in outpatient settings who receive hemodynamic monitoring by thoracic bioimpedance, the evidence includes uncontrolled prospective studies and case series. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. There is a lack of randomized controlled trial evidence evaluating whether the use of these technologies improves health outcomes over standard active management of heart failure patients. The case series have reported physiologic measurement-related outcomes and/or associations between monitoring information and heart failure exacerbations, but do not provide definitive evidence on device efficacy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Population reference No. 3

Inert Gas Rebreathing

Clinical Context and Test Purpose

The purpose of inert gas breathing in patients who have heart failure in an outpatient setting is (1) to guide volume management, (2) to identify physiologic changes that precede clinical symptoms and thus allow preventive interventions, and (3) to prevent hospitalizations.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is patients with chronic heart failure who are at risk of developing ADHF.

Interventions

The test being considered is inert gas breathing.

Inert gas rebreathing is based on the observation that the absorption and disappearance of a blood-soluble gas are proportional to cardiac blood flow. The patient is asked to breathe and rebreathe from a bag filled with oxygen mixed with a fixed proportion of 2 inert gases, typically nitrous oxide and sulfur hexafluoride. The nitrous oxide is soluble in blood and is therefore absorbed during the blood's passage through the lungs at a rate proportional to the blood flow. The sulfur hexafluoride is insoluble in blood and therefore stays in the gas phase and is used to determine the lung volume from which the soluble gas is removed. These gases and carbon dioxide are measured continuously and simultaneously at the mouthpiece.

Comparators

The comparator of interest is standard clinical care without testing. Decisions on guiding volume management are being made based on signs and symptoms.

Outcomes

The general outcomes of interest are the prevention of decompensation episodes, reduction in hospitalization and mortality, and improvement in quality of life.

Trials of using inert gas rebreathing for this population were not found. Generally, demonstration of outcomes over a 1-year period is meaningful for interventions.

Study Selection Criteria

Methodologically credible studies were selected using the following principles.

• Comparative controlled prospective trials were sought, with a preference for RCTs.

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse effects, single-arm studies that capture longer periods of follow-up and/or larger populations will be considered.

• Larger sample size studies and longer duration studies are preferred.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

No studies on the clinical validity were identified that would establish how the use of inert gas rebreathing measurements helps detect the likelihood of decompensation.

Section Summary: Clinically Valid

The clinical validity of using inert gas breathing for patients with chronic heart failure who are at risk of developing ADHF has not been established.

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

Direct Evidence

Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs.

No studies were identified that determined how the use of inert gas rebreathing measurements is associated with changes in patient management or evaluated the effects of this technology on patient outcomes.

Chain of Evidence

Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility. Because the clinical validity of using inert gas breathing has not been proved, a chain of evidence to support clinical utility cannot be constructed.

Section Summary: Clinically Valid

No studies of clinical utility were identified that determined how the use of inert gas breathing measurements in managing heart failure affects patient outcomes. It is unclear how such devices will improve patient outcomes.

For individuals who have heart failure in outpatient settings who receive hemodynamic monitoring with inert gas rebreathing, no studies have been identified on clinical validity or clinical utility. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Population reference No. 4

Noninvasive Left Ventricular End-Diastolic Pressure Estimation

Clinical Context and Test Purpose

The purpose of LVEDP estimation in patients who have heart failure in an outpatient setting is (1) to guide volume management, (2) to identify physiologic changes that precede clinical symptoms and thus allow preventive interventions, and (3) to prevent hospitalizations.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is patients with chronic heart failure who are at risk of developing ADHF.

Interventions

The test being considered is noninvasive LVEDP estimation.

LVEDP is elevated with acute decompensated heart failure. While direct catheter measurement of LVEDP is possible for patients undergoing cardiac catheterization for diagnostic or therapeutic reasons, its invasive nature precludes outpatient use. Noninvasive measurements of LVEDP have been developed based on the observation that arterial pressure during the strain phase of the Valsalva maneuver may directly reflect the LVEDP. Arterial pressure responses during repeated Valsalva maneuvers can be recorded and analyzed to produce values that correlate to the LVEDP.

Comparators

The comparator of interest is standard clinical care without testing. Decisions guiding volume management are being made based on signs and symptoms.

Outcomes

The general outcomes of interest are the prevention of decompensation episodes, reduction in hospitalization and mortality, and improvement in quality of life.

Trials of using noninvasive LVEDP estimation for this population were not found. Generally, demonstration of outcomes over a 1-year period is meaningful for interventions.

Study Selection Criteria

Methodologically credible studies were selected using the following principles.

• Comparative controlled prospective trials were sought, with a preference for RCTs.

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse effects, single-arm studies that capture longer periods of follow-up and/or larger populations will be considered.

• Larger sample size studies and longer duration studies are preferred.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Silber et al (2012) reported on finger photoplethysmography during the Valsalva maneuver performed in 33 patients before cardiac catheterization. .^40, LVEDP was measured via a catheter placed in the left ventricle and used as the reference standard. For identifying LVEDP greater than 15 mm Hg, finger photoplethysmography during the Valsalva maneuver was 85% sensitive (95% CI, 54% to 97%) and 80% specific (95% CI, 56% to 93%).

Section Summary: Clinically Valid

Only 1 study was identified assessing the use of LVEDP monitoring in this patient population; it reported an 85% sensitivity and an 80% specificity to detect LVEDP greater than 15 mm Hg.

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

Direct Evidence

Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs.

No studies were identified that determined how the use of noninvasive LVEDP estimation is associated with changes in patient management or evaluated the effects on patient outcomes.

Chain of Evidence

Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.

Because the clinical validity of using noninvasive LVEDP estimation has only been demonstrated in a small, single study, a chain of evidence to support clinical utility cannot be constructed.

Section Summary: Clinically Useful

No studies of clinical utility were identified that assessed how the use of noninvasive LVEDP estimation in managing heart failure affects patient outcomes. A chain of evidence on the clinical utility of noninvasive LVEDP estimation cannot be constructed because it is unclear how these devices will improve patient outcomes.

For individuals who have heart failure in outpatient settings who receive hemodynamic monitoring of arterial pressure during the Valsalva maneuver, a single study was identified. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, morbid events, hospitalizations, and treatment-related morbidity. The study assessed the use of LVEDP monitoring and reported an 85% sensitivity and an 80% specificity to detect LVEDP greater than 15 mm Hg. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American College of Cardiology et al

In 2017, the American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America (HFSA) issued joint guidelines on the management of heart failure that offered no recommendations for the use of ambulatory monitoring devices.^32,

In the 2022 update to the heart failure management guidelines, 2 recommendations were provided regarding remote hemodynamic monitoring in heart failure. These recommendations are summarized below in Table 14.

Table 14. 2022 ACC/AHA/HFSA Recommendation for Wearables and Remote Monitoring (including Telemonitoring and Device Monitoring)^42,

ACC: American College of Cardiology; AHA: American Heart Association; GDMT: guideline-directed medical therapy; HF: heart failure; HFSA: Heart Failure Society of America; NYHA: New York Heart Association; PA: pulmonary artery.Adapted from Heidenreich et al (2022)42,

National Institute for Health and Care Excellence

In 2021, the NICE issued a new interventional procedures guidance regarding the use of percutaneous implantation of pulmonary artery pressure sensors for monitoring the treatment of chronic heart failure.^40, The Institute's recommendation stated that "Evidence on the safety and efficacy of percutaneous implantation of pulmonary artery pressure sensors for monitoring treatment of chronic heart failure is adequate to support using this procedure provided that standard arrangements are in place for clinical governance, consent, and audit."

Heart Failure Society of America

In 2018, the Heart Failure Society of America Scientific Statements Committee (2018) published a white paper consensus statement on remote monitoring of patients with heart failure. .⁴⁴

The committee concluded that: "Based on available evidence, routine use of external RPM devices is not recommended. Implanted devices that monitor pulmonary arterial pressure and/or other parameters may be beneficial in selected patients or when used in structured programs, but the value of these devices in routine care requires further study."

U.S. Preventive Services Task Force Recommendations

Not applicable.

Medicare National Coverage

In 2014, the Centers for Medicare & Medicaid Services updated its 2006 decision memorandum on thoracic electrical bioimpedance.^31, Medicare's national coverage determination found thoracic bioimpedance to be reasonable and necessary for the following indications:

• Differentiation of cardiogenic from pulmonary causes of acute dyspnea;

• Optimization of atrioventricular interval for patients with atrioventricular sequential cardiac pacemakers;

• Monitoring of continuous inotropic therapy for patients with terminal heart failure;

• Evaluation for rejection in patients with a heart transplant as a predetermined alternative to myocardial biopsy; and

• Optimization of fluid management in patients with congestive heart failure.

While Medicare permits coverage of thoracic bioimpedance in these conditions, it has acknowledged that there is a "…general absence of studies evaluating the impact of using thoracic bioimpedance for managing patients with cardiac disease…." Medicare does not cover the use of thoracic bioimpedance in the management of hypertension due to inadequate evidence.

Medicare has also specified that thoracic bioimpedance is not covered for "the management of all forms of hypertension (with the exception of drug-resistant hypertension…)." Further, Medicare specified that:

"[Contractors] have discretion to determine whether the use of TEB [thoracic bioimpedance] for the management of drug-resistant hypertension is reasonable and necessary. Drug resistant hypertension is defined as failure to achieve goal blood pressure in patients who are adhering to full doses of an appropriate 3-drug regimen that includes a diuretic."

There is no Medicare national coverage determination on implantable direct pressure monitoring, inert gas rebreathing, and arterial pressure with Valsalva.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 14.

Table 15. Summary of Key Trials

NCT: national clinical trial.a Denotes industry-sponsored or cosponsored trial. 

References

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Codes

Applicable Modifiers

As per correct coding guidelines.

Policy History