Heart Failure, Heart Failure，Congestive, Heart Failure, Diastolic, Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure NYHA Class IV, Heart Failure, Systolic, Heart Failure; With Decompensation, Heart Failure With Normal Ejection Fraction, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Heart Failure, Hemodynamic Monitoring, CardioMEMS, Pulmonary Artery Pressure
Brief summary
The GUIDE-HF IDE clinical trial is intended to demonstrate the effectiveness of the CardioMEMS™ HF System in an expanded patient population including heart failure (HF) patients outside of the present indication, but at risk for future HF events or mortality.
Detailed description
The GUIDE-HF IDE clinical trial is intended to demonstrate the effectiveness of the CardioMEMS™ HF System in an expanded patient population including HF patients outside of the present indication, but at risk for future HF events or mortality. The trial includes patients with New York Heart Association (NYHA) Class II, III, or IV HF who have an elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or an elevated Brain Natriuretic Peptide (BNP)) and/or a prior HF hospitalization (HFH). The GUIDE-HF IDE trial will include approximately 3600 subjects at approximately 140 North American sites and consists of two arms: a Randomized Arm and a Single Arm.
Interventions
DEVICECardioMEMS™ HF System
The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF.
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis and treatment for heart failure (HF) (regardless of left ventricular ejection fraction (LVEF)) for \> 90 days prior to the date of consent: a. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines as standard-of-care for HF therapy in the United States, with any intolerance documented. 2. GUIDE-HF Randomized Arm Only: NYHA Class II, III or IV HF symptoms documented within 30 days prior to consent. 3. GUIDE-HF Single Arm Only: NYHA Class III HF symptoms documented within 30 days prior to consent. 4. HF hospitalization (HFH) within 12 months prior to consent and/or elevated N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) (or Brain Natriuretic Peptide (BNP)) within 30 days prior to consent defined as: 1. Subjects with LVEF ≤ 40%: NT-proBNP ≥ 1000 pg/mL (or BNP ≥ 250 pg/mL). 2. Subjects with LVEF \> 40%: NT-proBNP ≥ 700 pg/mL (or BNP ≥ 175 pg/mL). 3. Thresholds for NT-proBNP and BNP (for both LVEF ≤ 40% and LVEF \> 40%) will be corrected for body mass index (BMI) using a 4% reduction per BMI unit over 25 kg/m2 5. ≥ 18 years of age 6. Chest circumference of \< 65 inches, if BMI is \> 35 kg/m2 7. Written informed consent obtained from subject 8. Willing and able to upload pulmonary artery (PA) pressure information and comply with the follow-up requirements
Exclusion criteria
1. Intolerance to all neuro-hormonal antagonists (i.e., intolerance to angiotensin converting enzyme-inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin-neprilysin inhibitors (ARNi), hydralazine/isosorbide dinitrate and beta-blockers) 2. ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes) 3. Received or are likely to receive an advanced therapy (e.g., mechanical circulatory support or cardiac transplant) in the next 12 months 4. NYHA Class IV HF patients with: 1. Continuous or chronic use of scheduled intermittent inotropic therapy for HF and an INTERMACS level of ≤ 4, OR 2. Persistence of fluid overload with maximum (or dose equivalent) diuretic intervention 5. Glomerular Filtration Rate (eGFR) \< 25 mL/min and non-responsive to diuretic therapy, or receiving chronic dialysis 6. Inability to tolerate or receive dual antiplatelet therapy or anticoagulation therapy for one month post-implantation 7. Significant congenital heart disease that has not been repaired and would prevent implantation of the CardioMEMS™ PA Sensor 8. Implanted with mechanical right heart valve(s) 9. Unrepaired severe valvular disease 10. Pregnant or planning to become pregnant in the next 12 months 11. An active, ongoing infection, defined as being febrile, an elevated white blood cell count, on intravenous antibiotics, and/or positive cultures (blood, sputum or urine). 12. History of current or recurrent (≥ 2 episodes within 5 years prior to consent) pulmonary emboli and/or deep vein thrombosis 13. Major cardiovascular event (e.g., unstable angina, myocardial infarction, percutaneous coronary intervention, open heart surgery, or stroke, etc.) within 90 days prior to consent 14. Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to consent 15. Enrollment into another trial with an active treatment arm 16. Anticipated life expectancy of \< 12 months 17. Any condition that, in the opinion of the Investigator, would not allow for utilization of the CardioMEMS™ HF System to manage the subject using information gained from hemodynamic measurements to adjust medications, including the presence of unexpectedly severe pulmonary hypertension (e.g., trans-pulmonary gradient \>15) at implant right heart catheterization (RHC), a history of non-compliance, or any condition that would preclude CardioMEMS™ PA Sensor implantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality | 12 months post-implantation (395 days after implant date) | The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months). | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality | 12 months post-implantation (395 days after implant date) | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events |
| (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post-Implantation | The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events. |
| (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events. |
| (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months). | The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| (Single Arm) HFHs Post- vs. Pre-implantation [Previous HF Hospitalization Only Group] | 12 months post-implantation vs 12 months pre-implantation | The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation |
| (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | Baseline, 6, and 12 months post-implantation | Six Minute Hall Walk (6MHW) Test Distance |
| (Randomized Arm) Safety: Freedom From DSRCs | 12 months post-implantation | Freedom from device/system related complications (DSRCs) |
| (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits | 12 months post-implantation | The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months). | The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Single Arm) Intravenous Diuretic Visits | 12 months post-implantation | The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy |
| (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months). | The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy |
| (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 12 months post-implantation | The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy |
| (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy |
| (Single Arm) HFHs | 12 months post-implantation | The number of HFHs |
| (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months). | The number of heart failure hospitalizations (HFHs) |
| (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of heart failure hospitalizations (HFHs) |
| (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of heart failure hospitalizations (HFHs) |
| (Single Arm) All-cause Mortality | 12 months post-implantation | The number of deaths of any cause |
| (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months). | The number of deaths of any cause |
| (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of deaths of any cause |
| (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of deaths of any cause |
| (Single Arm) Safety: Freedom From DSRCs | 12 months post-implantation | Proportion of subjects with freedom from device/system related complications (DSRCs) |
| (Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP Only Group] | 12 months post-implantation vs 12 months pre-implantation | The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation |
| (Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP and Previous HF Hospitalization Group] | 12 months post-implantation vs 12 months pre-implantation | The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation |
| (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits | 12 months post-implantation | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis) | The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months). | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis) | 12 Months Post Implantation | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis) | 12 Months Post Implantation | The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events |
| (Randomized Arm) HFHs | 12 months post-implantation | The number of recurrent HFHs |
| (Randomized Arm) HFHs [Follow-up Based COVID-19 Sensitivity Analysis] | The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months). | The number of recurrent HFHs |
| (Randomized Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post-Implantation | The number of recurrent HFHs |
| (Randomized Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of recurrent HFHs |
| (Randomized Arm) Intravenous Diuretic Visits | 12 months post-implantation | The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy |
| (Randomized Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months). | The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy |
| (Randomized Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post Implantation | The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy |
| (Randomized Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post-Implantation | The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy |
| (Randomized Arm) All-cause Mortality | 12 months post-implantation | The number of deaths of any cause |
| (Randomized Arm) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months). | The number of deaths of any cause |
| (Randomized Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 12 Months Post-Implantation | The number of deaths of any cause |
| (Randomized Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 12 Months Post-Implantation | The number of deaths of any cause |
| (Randomized Arm) KCCQ-12 | Baseline, 6, and 12 months post-implantation | Health status as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life over a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status. Change from baseline KCCQ-12 scores were evaluated at 6 and 12-month visits. |
| (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | Baseline, 6, and 12 months post-implantation | Health status as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life over a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status. Descriptive statistics of KCCQ-12 scores at baseline, 6 and 12-month visits were reported. |
| (Randomized Arm) EQ-5D-5L | Baseline, 6, and 12 months post-implantation | Health status as assessed by the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire The EQ-5D-5L Questionnaire is a standardized measure of health status that consists of a descriptive system and a visual analog score (VAS). The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score represents a better quality of life. |
| (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | Baseline, 6, and 12 months post-implantation | Health status as assessed by the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire The EQ-5D-5L Questionnaire is a standardized measure of health status that consists of a descriptive system and a visual analog score (VAS). The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score represents a better quality of life. |
| (Randomized Arm) 6MHW Test | Baseline, 6, and 12 months post-implantation | Six Minute Hall Walk (6MHW) Test Distance |
Other
| Measure | Time frame | Description |
|---|---|---|
| (Randomized Arm) HFHs Post- vs. Pre-implantation [Control Group] | 12 months post-implantation vs 12 months pre-implantation | The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation |
| (Single Arm) KCCQ-12 [Mixed Model Analysis] | 6 months post-implantation | Health status as assessed by the KCCQ-12 The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life on a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status. |
| (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 6 months post-implantation | Health status as assessed by the EQ-5D-5L Questionnaire. The data represents the EQ Visual Analogue Scale (VAS) subscale. The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score for represents a better quality of life. |
| (Single Arm) 6MHW Test [Mixed Model Analysis] | 6 months post-implantation | 6MHW Test Distance |
| (Single Arm) Cardiovascular Mortality | 12 months post-implantation | The number of deaths of cardiovascular cause |
| (Single Arm) All-cause Hospitalizations | 12 months post-implantation | The number of hospitalizations of any cause |
| (Single Arm) Frequency of Subject PA Pressure Uploads - Daily Compliance | 12 months post-implantation | The frequency of subject uploads of PA pressure |
| (Single Arm) Frequency of Subject PA Pressure Uploads - Weekly Compliance | 12 months post-implantation | The frequency of subject uploads of PA pressure |
| (Single Arm) HF Medication Changes | 12 months post-implantation | The number of changes in HF medications |
| (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Baseline through 12 months post-implantation | Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using a mixed linear model at fixed time points (Baseline, 6 months, and 12 months) producing least-squares means. |
| (Single Arm) PA Pressure Measurements [AUC Analysis] | Baseline through 12 months post-implantation | Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using area under the curve (AUC) analysis of PA pressure across the full follow-up period |
| (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | 6 months post-implantation | Either change in N-terminal pro-brain natriuretic peptide (NT-proBNP) or Brain natriuretic peptide (BNP) measurements at 6 months visits from baseline. |
| (Randomized Arm) BNP | 6 months post-implantation | Change in BNP measurements from baseline |
| (Randomized Arm) PA Pressure Measurements [AUC Analysis] | Baseline through 12 months post-implantation | Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using an area under the curve (AUC) analysis of change from baseline on all PA pressure readings through 12 months. |
| (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | Baseline through 12 months post-implantation | Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using a mixed linear model at fixed time points (Baseline, 6 months, and 12 months) producing least-squares means. |
| (Randomized Arm) HF Medication Changes | 12 months post-implantation | The number of changes in HF medications |
| (Randomized Arm) Frequency of Subject PA Pressure Uploads | 12 months post-implantation | The frequency of subject uploads of PA pressure |
| (Randomized Arm) Cardiovascular Mortality | 12 months post-implantation | The number of deaths with cardiovascular cause |
| (Randomized Arm) All-cause Hospitalizations | 12 months post-implantation | The number of hospitalizations of any cause |
| (Randomized Arm) HFHs Post- vs. Pre-implantation [Treatment Group] | 12 months post-implantation vs 12 months pre-implantation | The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation in the Treatment group |
| (Randomized Arm) NT-proBNP | 6 months post-implantation | Change in NT-proBNP measurements from baseline |
Countries
Canada, United States
Participant flow
Recruitment details
Randomized Arm enrolled 1022 subjects across 118 sites, of which 1000 are endpoint-contributing (successfully implanted and randomized). Subject enrollment took place between March 2018 and December 2019, with the last follow-up completed in January 2021. Single Arm enrolled 1401 subjects across 119 sites, of which 1358 are endpoint-contributing (successfully implanted). Subject enrollment took place between March 2018 and April 2022, with the last follow-up completed in May 2023.
Pre-assignment details
22 subjects were not randomized in the Randomized Arm and 43 subjects were not assigned to the Single Arm due to unsuccessful implantation attempts.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Arm - Treatment Group Management of subjects based on pulmonary artery (PA) pressure information derived from the CardioMEMS™ HF System.
All subjects will receive a CardioMEMS™ HF System.
CardioMEMS™ HF System: The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF. | 497 |
| Randomized Arm - Control Group Management of subjects per standard of care (signs, symptoms, weight etc.) without knowledge of PA pressure information derived from the CardioMEMS™ HF System.
All subjects will receive a CardioMEMS™ HF System.
CardioMEMS™ HF System: The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF. | 503 |
| Single Arm Management of subjects based on PA pressure information derived from the CardioMEMS™ HF System.
All subjects will receive a CardioMEMS™ HF System.
CardioMEMS™ HF System: The CardioMEMS™ HF System is comprised of a lead-less, battery-less pressure sensor permanently implanted in the PA, which remotely transmits PA pressure measurements from the patient's home to a secure website. Healthcare professionals are able to access these measurements and associated waveforms to remotely guide individualization of medical management for their patients with chronic HF. | 1,358 |
| Total | 2,358 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 40 | 37 | 190 |
| Overall Study | Lost to Follow-up | 3 | 9 | 15 |
| Overall Study | Non-Compliance | 6 | 6 | 31 |
| Overall Study | Subject In Hospice/Relocated/Severe COVID-19/On Transplant List/PI Discretion | 7 | 10 | 14 |
| Overall Study | Withdrawal by Subject | 9 | 19 | 32 |
Baseline characteristics
| Characteristic | Randomized Arm - Treatment Group | Total | Single Arm | Randomized Arm - Control Group |
|---|---|---|---|---|
| 6-minute Walk Test (6MHW) | 235.2 meters STANDARD_DEVIATION 120.2 | 212.2 meters STANDARD_DEVIATION 126.2 | 196.9 meters STANDARD_DEVIATION 127.4 | 229.6 meters STANDARD_DEVIATION 123 |
| ACE-Inhibitor or ARB or ARNi | 319 Participants | 1341 Participants | 702 Participants | 320 Participants |
| Age, Continuous | 69.2 years STANDARD_DEVIATION 11.1 | 69.9 years STANDARD_DEVIATION 11 | 70.5 years STANDARD_DEVIATION 10.9 | 69.2 years STANDARD_DEVIATION 11 |
| Ambulatory Heart Rate during First Week | 78.8 beats per minute (bpm) STANDARD_DEVIATION 11.7 | 79.2 beats per minute (bpm) STANDARD_DEVIATION 11.8 | 79.3 beats per minute (bpm) STANDARD_DEVIATION 11.9 | 79.4 beats per minute (bpm) STANDARD_DEVIATION 11.9 |
| Ambulatory Hemodynamics during First Week PA Diastolic Pressure | 22.4 mmHg STANDARD_DEVIATION 7.8 | 22.8 mmHg STANDARD_DEVIATION 7.5 | 23.0 mmHg STANDARD_DEVIATION 7.4 | 22.7 mmHg STANDARD_DEVIATION 7.4 |
| Ambulatory Hemodynamics during First Week PA Mean Pressure | 31.8 mmHg STANDARD_DEVIATION 10.2 | 32.3 mmHg STANDARD_DEVIATION 9.8 | 32.6 mmHg STANDARD_DEVIATION 9.7 | 31.9 mmHg STANDARD_DEVIATION 9.6 |
| Ambulatory Hemodynamics during First Week PA Systolic Pressure | 46.3 mmHg STANDARD_DEVIATION 14.4 | 46.9 mmHg STANDARD_DEVIATION 13.9 | 47.4 mmHg STANDARD_DEVIATION 13.9 | 46.2 mmHg STANDARD_DEVIATION 13.3 |
| ARNi | 145 Participants | 602 Participants | 318 Participants | 139 Participants |
| Beta Blocker | 444 Participants | 2012 Participants | 1126 Participants | 442 Participants |
| Body Mass Index | 32.9 kg/m2 STANDARD_DEVIATION 8.3 | 33.8 kg/m2 STANDARD_DEVIATION 8.7 | 34.0 kg/m2 STANDARD_DEVIATION 8.8 | 33.8 kg/m2 STANDARD_DEVIATION 8.4 |
| Cardiac index | 2.27 L/min/m2 STANDARD_DEVIATION 1.11 | 2.24 L/min/m2 STANDARD_DEVIATION 0.77 | 2.24 L/min/m2 STANDARD_DEVIATION 0.66 | 2.19 L/min/m2 STANDARD_DEVIATION 0.63 |
| Cardiac output | 4.83 L/min STANDARD_DEVIATION 2.62 | 4.78 L/min STANDARD_DEVIATION 1.81 | 4.80 L/min STANDARD_DEVIATION 1.55 | 4.70 L/min STANDARD_DEVIATION 1.46 |
| Diastolic blood pressure | 69.2 mmHg STANDARD_DEVIATION 10.8 | 68.3 mmHg STANDARD_DEVIATION 10.8 | 67.7 mmHg STANDARD_DEVIATION 10.8 | 69.0 mmHg STANDARD_DEVIATION 10.8 |
| Diuretic | 474 Participants | 2274 Participants | 1322 Participants | 478 Participants |
| Enrollment Type - Prior Elevated NT-proBNP/BNP | 230 Participants | 894 Participants | 452 Participants | 212 Participants |
| Enrollment Type - Prior Heart Failure Hospitalization and Elevated NT-proBNP/BNP | 97 Participants | 539 Participants | 343 Participants | 99 Participants |
| Enrollment Type - Prior Heart Failure Hospitalization Only | 170 Participants | 910 Participants | 549 Participants | 191 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 94 Participants | 61 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 477 Participants | 2243 Participants | 1283 Participants | 483 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 21 Participants | 14 Participants | 3 Participants |
| Heart rate | 73.8 beats per minute (bpm) STANDARD_DEVIATION 12.5 | 74.1 beats per minute (bpm) STANDARD_DEVIATION 12.5 | 74.2 beats per minute (bpm) STANDARD_DEVIATION 12.5 | 74.2 beats per minute (bpm) STANDARD_DEVIATION 12.3 |
| Hydralazine | 81 Participants | 361 Participants | 200 Participants | 80 Participants |
| KCCQ-12 Score | 54.9 scores on a scale STANDARD_DEVIATION 24.3 | 51.4 scores on a scale STANDARD_DEVIATION 23.2 | 48.8 scores on a scale STANDARD_DEVIATION 22.3 | 54.9 scores on a scale STANDARD_DEVIATION 23.8 |
| Laboratory Analyses - Brain Natriuretic Peptide (BNP) | 520.7 pg/mL STANDARD_DEVIATION 689.2 | 525.4 pg/mL STANDARD_DEVIATION 718.3 | 517 pg/mL STANDARD_DEVIATION 618.8 | 552.4 pg/mL STANDARD_DEVIATION 954 |
| Laboratory Analyses - Estimated glomerular filtration rate | 54.3 ml/min/1.73m2 STANDARD_DEVIATION 21.3 | 52.2 ml/min/1.73m2 STANDARD_DEVIATION 21.2 | 51.2 ml/min/1.73m2 STANDARD_DEVIATION 21.3 | 52.8 ml/min/1.73m2 STANDARD_DEVIATION 20.8 |
| Laboratory Analyses - N-terminal pro-B-type natriuretic peptide (NT-proBNP) | 2460 pg/mL STANDARD_DEVIATION 3707 | 2395 pg/mL STANDARD_DEVIATION 3423 | 2446 pg/mL STANDARD_DEVIATION 3521 | 2183 pg/mL STANDARD_DEVIATION 2803 |
| Laboratory Analyses - Serum creatinine level | 128.5 μmol/L STANDARD_DEVIATION 44.5 | 132.8 μmol/L STANDARD_DEVIATION 48.2 | 134.1 μmol/L STANDARD_DEVIATION 49.4 | 133.5 μmol/L STANDARD_DEVIATION 48.5 |
| Left ventricular ejection fraction | 39.4 % STANDARD_DEVIATION 17.3 | 42.0 % STANDARD_DEVIATION 17.1 | 43.5 % STANDARD_DEVIATION 17 | 40.7 % STANDARD_DEVIATION 16.9 |
| Left ventricular ejection fraction > 40% | 224 Participants | 1221 Participants | 752 Participants | 245 Participants |
| Medical History - Atrial flutter or fibrillation | 300 Participants | 1435 Participants | 844 Participants | 291 Participants |
| Medical History - Cerebrovascular accident | 66 Participants | 317 Participants | 186 Participants | 65 Participants |
| Medical History - Diabetes | 243 Participants | 1189 Participants | 685 Participants | 261 Participants |
| Medical History - Ischemic etiology | 207 Participants | 886 Participants | 489 Participants | 190 Participants |
| Medical History - Previous coronary artery bypass grafting | 135 Participants | 602 Participants | 331 Participants | 136 Participants |
| Medical History - Previous myocardial infarction | 144 Participants | 661 Participants | 359 Participants | 158 Participants |
| Medical History - Previous percutaneous coronary intervention | 165 Participants | 702 Participants | 379 Participants | 158 Participants |
| Mineralocorticoid Receptor Antagonist | 237 Participants | 1066 Participants | 613 Participants | 216 Participants |
| New York Heart Association (NYHA) Class Class II | 146 Participants | 296 Participants | 0 Participants | 150 Participants |
| New York Heart Association (NYHA) Class Class III | 322 Participants | 2006 Participants | 1356 Participants | 328 Participants |
| New York Heart Association (NYHA) Class Class IV | 29 Participants | 55 Participants | 1 Participants | 25 Participants |
| Nitrate | 99 Participants | 448 Participants | 246 Participants | 103 Participants |
| PA Diastolic Pressure | 18.9 mmHg STANDARD_DEVIATION 8 | 19.4 mmHg STANDARD_DEVIATION 7.7 | 19.7 mmHg STANDARD_DEVIATION 7.6 | 18.8 mmHg STANDARD_DEVIATION 7.7 |
| PA Mean Pressure | 29.2 mmHg STANDARD_DEVIATION 9.5 | 29.8 mmHg STANDARD_DEVIATION 9.7 | 30.2 mmHg STANDARD_DEVIATION 9.7 | 29.4 mmHg STANDARD_DEVIATION 10 |
| Pulmonary artery (PA) systolic pressure | 44.9 mmHg STANDARD_DEVIATION 13.9 | 46.0 mmHg STANDARD_DEVIATION 14.8 | 46.7 mmHg STANDARD_DEVIATION 15.1 | 45.2 mmHg STANDARD_DEVIATION 14.6 |
| Pulmonary capillary wedge pressure | 17.3 mmHg STANDARD_DEVIATION 8 | 17.8 mmHg STANDARD_DEVIATION 7.7 | 18.0 mmHg STANDARD_DEVIATION 7.5 | 17.6 mmHg STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 6 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 13 Participants | 12 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 86 Participants | 367 Participants | 188 Participants | 93 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 32 Participants | 23 Participants | 3 Participants |
| Race (NIH/OMB) White | 403 Participants | 1932 Participants | 1125 Participants | 404 Participants |
| Sex: Female, Male Female | 187 Participants | 959 Participants | 584 Participants | 188 Participants |
| Sex: Female, Male Male | 310 Participants | 1399 Participants | 774 Participants | 315 Participants |
| SGLT2 Inhibitor | 2 Participants | 119 Participants | 115 Participants | 2 Participants |
| Systolic blood pressure | 121.6 mmHg STANDARD_DEVIATION 19.1 | 120.9 mmHg STANDARD_DEVIATION 18.8 | 120.7 mmHg STANDARD_DEVIATION 19 | 120.8 mmHg STANDARD_DEVIATION 18.1 |
| Treatment History - Previous cardiac resynchronization therapy | 142 Participants | 672 Participants | 367 Participants | 163 Participants |
| Treatment History - Previous implantation of defibrillator | 213 Participants | 875 Participants | 457 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 40 / 497 | 37 / 503 | 190 / 1,358 |
| other Total, other adverse events | 15 / 497 | 20 / 503 | 33 / 1,358 |
| serious Total, serious adverse events | 283 / 497 | 272 / 503 | 820 / 1,358 |
Outcome results
Primary
(Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality
The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events
Time frame: 12 months post-implantation (395 days after implant date)
Population: The primary endpoint was analyzed in the endpoint-contributing population, which included subjects that were successfully implanted and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality | 0.563 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality | 0.640 events per patient-year |
p-value: 0.162495% CI: [0.74, 1.05]Anderson-Gill model (robust sandwich)
Primary
(Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis]
The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events.
Time frame: 12 Months Post-Implantation
Population: The primary endpoint was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. All subjects were enrolled before COVID-19 period (March 13, 2020). The event based COVID-19 sensitivity analysis compares treatment effect by excluding events adjudicated as either related or possible related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.563 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.633 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.558 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.619 events per patient-year |
Primary
(Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis]
The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events.
Time frame: The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months).
Population: The primary endpoint limited to the follow-up period occurring Pre-COVID-19 or During COVID-19 was analyzed in the endpoint-contributing population including subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. All subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate in the Andersen-Gill model. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.553 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.682 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.597 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.536 events per patient-year |
Primary
(Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis]
The composite of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of heart failure (HF) emergency department/hospital outpatient observation visits for intravenous diuretic therapy (ED/OP) 3. The number of deaths of any cause added together with equal weighting into a total number of events.
Time frame: 12 Months Post Implantation
Population: The primary endpoint was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.710 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.864 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.508 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.539 events per patient-year |
Primary
(Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events
Time frame: 12 months post-implantation (395 days after implant date)
Population: The primary endpoint was compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality | 0.394 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality | 0.771 events per patient-year |
90% CI: [0.44, 0.6]
Primary
(Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis]
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events
Time frame: 12 Months Post Implantation
Population: The primary endpoint was compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group, but excluding primary endpoint events adjudicated as either related or possibly related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.381 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.746 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.377 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.737 events per patient-year |
Primary
(Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis]
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events
Time frame: Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months).
Population: The primary endpoint limited to the follow-up period occurring Prior to COVID-19 or During COVID-19 was compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group. Subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.263 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.861 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.418 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.744 events per patient-year |
Primary
(Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis]
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy 3. The number of deaths of any cause added together with equal weighting into a total number of events
Time frame: 12 Months Post Implantation
Population: The primary endpoint was compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.582 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 1.853 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.391 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs, (2) Intravenous Diuretic Visits, and (3) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.698 events per patient-year |
Secondary
(Randomized Arm) 6MHW Test
Six Minute Hall Walk (6MHW) Test Distance
Time frame: Baseline, 6, and 12 months post-implantation
Population: Subjects that have a baseline value and at least one value at either 6- or 12-month visits were analyzed. Subjects who were unable to walk due to heart failure symptoms were assigned zero meters. The Least Square Means (LSM) difference in 6MHW distance at 6 months and 12 months from baseline in both Treatment and Control groups during the overall follow-up period were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) 6MHW Test | -1.13 meters, m | Standard Error 5.25 |
| Randomized Arm - Control Group | (Randomized Arm) 6MHW Test | 3.01 meters, m | Standard Error 5.16 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) 6MHW Test | -13.02 meters, m | Standard Error 5.54 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) 6MHW Test | -10.09 meters, m | Standard Error 5.5 |
p-value: 0.574195% CI: [-10.32, 18.6]t-test, 1 sided
p-value: 0.707795% CI: [-12.41, 18.27]t-test, 1 sided
Secondary
(Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis)
Six Minute Hall Walk (6MHW) Test Distance
Time frame: Baseline, 6, and 12 months post-implantation
Population: The 6MHW distance at baseline, 6 months, and 12 months were analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 227 meters, m | Standard Deviation 117.8 |
| Randomized Arm - Control Group | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 243.8 meters, m | Standard Deviation 124.7 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 239.3 meters, m | Standard Deviation 123.5 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 260.8 meters, m | Standard Deviation 120.8 |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 230.4 meters, m | Standard Deviation 133.2 |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 245.1 meters, m | Standard Deviation 136.1 |
| Randomized Arm - Treatment Group (Baseline) [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 240.2 meters, m | Standard Deviation 121.5 |
| Randomized Arm - Control Group (Baseline) [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 220.6 meters, m | Standard Deviation 121.3 |
| Randomized Arm - Treatment Group (6 Month) [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 249.8 meters, m | Standard Deviation 129.1 |
| Randomized Arm - Control Group (6 Month) [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 244.7 meters, m | Standard Deviation 135.6 |
| Randomized Arm - Treatment Group (12 Month) [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 246.0 meters, m | Standard Deviation 130 |
| Randomized Arm - Control Group (12 Month) [During COVID-19] | (Randomized Arm) 6MHW Test (Subject Based COVID-19 Sensitivity Analysis) | 230.7 meters, m | Standard Deviation 135.3 |
Secondary
(Randomized Arm) All-cause Mortality
The number of deaths of any cause
Time frame: 12 months post-implantation
Population: The number of death events of any cause were analyzed in the full cohort of endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) All-cause Mortality | 0.094 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) All-cause Mortality | 0.086 events per patient-year |
p-value: 0.711995% CI: [0.7, 1.7]Anderson-Gill model (robust sandwich)
Secondary
(Randomized Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis]
The number of deaths of any cause
Time frame: 12 Months Post-Implantation
Population: The mortality events were analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. All subjects were enrolled before COVID-19 period (March 13, 2020). The event based COVID-19 sensitivity analysis compares treatment effect by excluding events adjudicated as either related or possible related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.094 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.086 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.090 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.079 events per patient-year |
Secondary
(Randomized Arm) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis]
The number of deaths of any cause
Time frame: The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months).
Population: The number of death events of any cause limited to the follow-up period occurring prior to and during COVID-19 were analyzed in the full cohort of endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized. All subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.110 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.088 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.067 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) All-cause Mortality [Follow-up Based COVID-19 Sensitivity Analysis] | 0.085 events per patient-year |
Secondary
(Randomized Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis]
The number of deaths of any cause
Time frame: 12 Months Post-Implantation
Population: The mortality events were analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.200 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.161 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.044 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.053 events per patient-year |
Secondary
(Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: 12 months post-implantation
Population: The secondary outcome (composite of HFH and ED/OP visits) was analyzed in the full cohort of endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits | 0.474 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits | 0.557 events per patient-year |
p-value: 0.095895% CI: [0.7, 1.03]Anderson-Gill model (robust sandwich)
Secondary
(Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis)
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: 12 Months Post Implantation
Population: The composite outcome was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. All subjects were enrolled before COVID-19 period (March 13, 2020). The event based COVID-19 sensitivity analysis compares treatment effect by excluding events adjudicated as either related or possible related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis) | 0.474 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis) | 0.551 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis) | 0.472 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis) | 0.545 events per patient-year |
Secondary
(Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis)
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months).
Population: The secondary outcome (composite of HFH and ED/OP visits) limited to the follow-up period occurring prior to COVID-19 or during COVID-19 were analyzed in the full cohort of endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized. All subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis) | 0.450 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis) | 0.595 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis) | 0.539 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis) | 0.455 events per patient-year |
Secondary
(Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis)
The composite outcome of: 1. The number of recurrent heart failure hospitalizations (HFHs) 2. The number of emergency department/hospital outpatient observation visits (ED/OP) for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: 12 Months Post Implantation
Population: The secondary outcome (composite of HFH and ED/OP visits) was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis) | 0.529 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis) | 0.729 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis) | 0.465 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis) | 0.488 events per patient-year |
Secondary
(Randomized Arm) EQ-5D-5L
Health status as assessed by the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire The EQ-5D-5L Questionnaire is a standardized measure of health status that consists of a descriptive system and a visual analog score (VAS). The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score represents a better quality of life.
Time frame: Baseline, 6, and 12 months post-implantation
Population: Subjects that have a baseline value and at least one value at either 6- or 12-month visits were analyzed. The Least Square Means (LSM) difference in EQ-5D-5L VAS at 6 months and 12 months visits from baseline during overall follow-up for Treatment and Control groups were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) EQ-5D-5L | 3.18 scores on a scale | Standard Error 0.97 |
| Randomized Arm - Control Group | (Randomized Arm) EQ-5D-5L | 3.20 scores on a scale | Standard Error 0.97 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) EQ-5D-5L | 1.02 scores on a scale | Standard Error 0.99 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) EQ-5D-5L | 2.50 scores on a scale | Standard Error 1 |
p-value: 0.990195% CI: [-2.68, 2.71]t-test, 1 sided
p-value: 0.294795% CI: [-1.29, 4.24]t-test, 1 sided
Secondary
(Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis)
Health status as assessed by the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Questionnaire The EQ-5D-5L Questionnaire is a standardized measure of health status that consists of a descriptive system and a visual analog score (VAS). The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score represents a better quality of life.
Time frame: Baseline, 6, and 12 months post-implantation
Population: The EQ-5D-5L score at baseline, 6 months, and 12 months were analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 66.5 scores on a scale | Standard Deviation 20.3 |
| Randomized Arm - Control Group | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 67.3 scores on a scale | Standard Deviation 18.9 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 71.7 scores on a scale | Standard Deviation 18.3 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 71.2 scores on a scale | Standard Deviation 20 |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 68.3 scores on a scale | Standard Deviation 20.9 |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 71.5 scores on a scale | Standard Deviation 18.5 |
| Randomized Arm - Treatment Group (Baseline) [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 66.2 scores on a scale | Standard Deviation 18.1 |
| Randomized Arm - Control Group (Baseline) [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 63.4 scores on a scale | Standard Deviation 19.7 |
| Randomized Arm - Treatment Group (6 Month) [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 69.5 scores on a scale | Standard Deviation 19.2 |
| Randomized Arm - Control Group (6 Month) [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 67.1 scores on a scale | Standard Deviation 20.6 |
| Randomized Arm - Treatment Group (12 Month) [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 68.8 scores on a scale | Standard Deviation 19.8 |
| Randomized Arm - Control Group (12 Month) [During COVID-19] | (Randomized Arm) EQ-5D-5L (Subject Based COVID-19 Sensitivity Analysis) | 66.4 scores on a scale | Standard Deviation 21.9 |
Secondary
(Randomized Arm) HFHs
The number of recurrent HFHs
Time frame: 12 months post-implantation
Population: The number of recurrent HFHs were analyzed within the full cohort of endpoint-contributing population, which includes subjects of NYHA class II/III/IV that were successfully implanted and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HFHs | 0.410 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) HFHs | 0.497 events per patient-year |
p-value: 0.064495% CI: [0.68, 1.01]Anderson-Gill model (robust sandwich)
Secondary
(Randomized Arm) HFHs [Event Based COVID-19 Sensitivity Analysis]
The number of recurrent HFHs
Time frame: 12 Months Post Implantation
Population: The number of recurrent HFHs was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. All subjects were enrolled before COVID-19 period (March 13, 2020). The event based COVID-19 sensitivity analysis compares treatment effect by excluding events adjudicated as either related or possible related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.411 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.490 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.409 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.484 events per patient-year |
Secondary
(Randomized Arm) HFHs [Follow-up Based COVID-19 Sensitivity Analysis]
The number of recurrent HFHs
Time frame: The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months).
Population: The number of recurrent HFHs limited to the follow-up period occurring prior to COVID-19 or during COVID-19 were analyzed within the full cohort of endpoint-contributing population, which includes subjects of NYHA class II/III/IV that were successfully implanted and randomized. All subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HFHs [Follow-up Based COVID-19 Sensitivity Analysis] | 0.380 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) HFHs [Follow-up Based COVID-19 Sensitivity Analysis] | 0.525 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) HFHs [Follow-up Based COVID-19 Sensitivity Analysis] | 0.490 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) HFHs [Follow-up Based COVID-19 Sensitivity Analysis] | 0.414 events per patient-year |
Secondary
(Randomized Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis]
The number of recurrent HFHs
Time frame: 12 Months Post-Implantation
Population: The number of recurrent HFHs was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.467 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.666 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.399 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.428 events per patient-year |
Secondary
(Randomized Arm) Intravenous Diuretic Visits
The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy
Time frame: 12 months post-implantation
Population: The number of ED/OP visits were analyzed in the full cohort of endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Intravenous Diuretic Visits | 0.065 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Intravenous Diuretic Visits | 0.063 events per patient-year |
p-value: 0.886795% CI: [0.61, 1.77]Anderson-Gill model (robust sandwich)
Secondary
(Randomized Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis]
The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy
Time frame: 12 Months Post-Implantation
Population: The outcome was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. All subjects were enrolled before COVID-19 period (March 13, 2020). The event based COVID-19 sensitivity analysis compares treatment effect by excluding events adjudicated as either related or possible related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.065 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.063 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.065 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.063 events per patient-year |
Secondary
(Randomized Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis]
The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy
Time frame: The COVID-19 pandemic occurred during follow-up after enrollment of all subjects. Events were analyzed through March 13, 2020 for pre-COVID-19 (median follow-up: 8.4 months) and after March 13, 2020 for during COVID-19 (median follow-up: 5.2 months).
Population: The number of ED/OP visits limited to the follow-up period occurring prior to and during COVID-19 were analyzed in the full cohort of endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized. All subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.074 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.073 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.048 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.041 events per patient-year |
Secondary
(Randomized Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis]
The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy
Time frame: 12 Months Post Implantation
Population: The outcome was analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.067 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.071 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.067 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.060 events per patient-year |
Secondary
(Randomized Arm) KCCQ-12
Health status as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life over a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status. Change from baseline KCCQ-12 scores were evaluated at 6 and 12-month visits.
Time frame: Baseline, 6, and 12 months post-implantation
Population: Subjects that have a baseline value and at least one value at either 6- or 12-month visits were analyzed. The Least Square Means (LSM) difference in KCCQ-12 Overall Summary Score at 6 months, and 12 months visits from baseline during overall follow-up in Treatment and Control groups were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) KCCQ-12 | 7.36 scores on a scale | Standard Error 1.01 |
| Randomized Arm - Control Group | (Randomized Arm) KCCQ-12 | 6.01 scores on a scale | Standard Error 1.02 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) KCCQ-12 | 4.77 scores on a scale | Standard Error 1.03 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) KCCQ-12 | 4.14 scores on a scale | Standard Error 1.05 |
p-value: 0.348495% CI: [-4.16, 1.47]t-test, 1 sided
p-value: 0.668495% CI: [-3.51, 2.26]t-test, 1 sided
Secondary
(Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis)
Health status as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life over a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status. Descriptive statistics of KCCQ-12 scores at baseline, 6 and 12-month visits were reported.
Time frame: Baseline, 6, and 12 months post-implantation
Population: The KCCQ-12 score at baseline, 6 months, and 12 months were analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV that were successfully implanted and randomized into Treatment or Control groups. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 54.8 scores on a scale | Standard Deviation 25.4 |
| Randomized Arm - Control Group | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 56.4 scores on a scale | Standard Deviation 23.9 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 65.1 scores on a scale | Standard Deviation 24.3 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 63.6 scores on a scale | Standard Deviation 24.6 |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 62.0 scores on a scale | Standard Deviation 24 |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 62.9 scores on a scale | Standard Deviation 22.2 |
| Randomized Arm - Treatment Group (Baseline) [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 55.0 scores on a scale | Standard Deviation 23.6 |
| Randomized Arm - Control Group (Baseline) [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 53.9 scores on a scale | Standard Deviation 23.6 |
| Randomized Arm - Treatment Group (6 Month) [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 62.5 scores on a scale | Standard Deviation 24.3 |
| Randomized Arm - Control Group (6 Month) [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 60.3 scores on a scale | Standard Deviation 24.7 |
| Randomized Arm - Treatment Group (12 Month) [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 61.3 scores on a scale | Standard Deviation 24.7 |
| Randomized Arm - Control Group (12 Month) [During COVID-19] | (Randomized Arm) KCCQ-12 (Subject Based COVID-19 Sensitivity Analysis) | 58.2 scores on a scale | Standard Deviation 24.7 |
Secondary
(Randomized Arm) Safety: Freedom From DSRCs
Freedom from device/system related complications (DSRCs)
Time frame: 12 months post-implantation
Population: The overall freedom from DSRCs across the endpoint-contributing population were analyzed. The analysis population included all subjects in the efficacy population of the Randomized Arm (i.e. Randomized to Treatment and Control group).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Safety: Freedom From DSRCs | 494 Participants |
| Randomized Arm - Control Group | (Randomized Arm) Safety: Freedom From DSRCs | 498 Participants |
Secondary
(Single Arm) All-cause Mortality
The number of deaths of any cause
Time frame: 12 months post-implantation
Population: The secondary endpoint was analyzed in the endpoint-contributing populations, which consists of subjects with successful implantation in three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. Annualized event rate was estimated from the Andersen-Gill model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) All-cause Mortality | 0.113 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) All-cause Mortality | 0.146 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) All-cause Mortality | 0.243 events per patient-year |
p-value: 0.0001ANOVA
Secondary
(Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis]
The number of deaths of any cause
Time frame: 12 Months Post Implantation
Population: The event was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization, but excluding events adjudicated as either related or possibly related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.105 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.125 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.231 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.105 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.123 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) All-cause Mortality [Event Based COVID-19 Sensitivity Analysis] | 0.227 events per patient-year |
Secondary
(Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis]
The number of deaths of any cause
Time frame: Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months).
Population: The event limited to the follow-up period occurring prior to COVID-19 or during COVID-19 was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. Subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.050 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.182 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.272 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.123 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.135 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) All-cause Mortality [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.233 events per patient-year |
Secondary
(Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis]
The number of deaths of any cause
Time frame: 12 Months Post Implantation
Population: The HFH event was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.147 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.384 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.583 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.113 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.120 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) All-cause Mortality [Subject Based COVID-19 Sensitivity Analysis] | 0.202 events per patient-year |
Secondary
(Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits
The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: 12 months post-implantation
Population: The secondary endpoint was compared between subjects qualifying with elevated NT-proBNP/BNP levels only and subjects qualifying with a prior HF hospitalization only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits | 0.288 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits | 0.630 events per patient-year |
90% CI: [0.38, 0.55]
Secondary
(Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis]
The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: 12 Months Post Implantation
Population: The results were compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group, but excluding primary endpoint events adjudicated as either related or possibly related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.282 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.624 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.277 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.617 events per patient-year |
Secondary
(Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis]
The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months).
Population: The secondary outcome events limited to the follow-up period were compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group. Subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.211 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.677 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.303 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.616 events per patient-year |
Secondary
(Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis]
The composite outcome of: 1. The number of recurrent HFHs 2. The number of emergency department/hospital outpatient observation visits for intravenous diuretic therapy added together with equal weighting into a total number of events
Time frame: 12 Months Post Implantation
Population: The results were compared between subjects in the qualifying with elevated NT-proBNP/BNP levels only group and subjects in the qualifying with prior HF hospitalization only group. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.436 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 1.520 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.286 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Composite Outcome of (1) HFHs and (2) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.583 events per patient-year |
Secondary
(Single Arm) HFHs
The number of HFHs
Time frame: 12 months post-implantation
Population: The secondary endpoint was analyzed in the endpoint-contributing populations, which consists of subjects with successful implantation in three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. Annualized event rate was estimated from the Andersen-Gill model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs | 0.263 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs | 0.557 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HFHs | 0.797 events per patient-year |
p-value: <0.0001ANOVA
Secondary
(Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis]
The number of heart failure hospitalizations (HFHs)
Time frame: 12 Months Post Implantation
Population: The HFH event was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization, but excluding events adjudicated as either related or possibly related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.257 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.552 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.790 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.252 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.545 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) HFHs [Event Based COVID-19 Sensitivity Analysis] | 0.749 events per patient-year |
Secondary
(Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis]
The number of heart failure hospitalizations (HFHs)
Time frame: Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months).
Population: The secondary outcome events limited to the follow-up period occurring prior to COVID-19 or during COVID-19 was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. Subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.214 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.804 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | 1.211 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.280 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.529 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) HFHs [Follow-Up Based COVID-19 Sensitivity Analysis] | 0.732 events per patient-year |
Secondary
(Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP and Previous HF Hospitalization Group]
The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation
Time frame: 12 months post-implantation vs 12 months pre-implantation
Population: All subjects met qualification criteria of elevated NT-proBNP/BNP and previous HF hospitalization and had successful implantation of CardioMEMS™ HF System.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP and Previous HF Hospitalization Group] | 1.380 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP and Previous HF Hospitalization Group] | 0.874 events per patient-year |
p-value: <0.00195% CI: [0.53, 0.76]Anderson-Gill model (robust sandwich)
Secondary
(Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP Only Group]
The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation
Time frame: 12 months post-implantation vs 12 months pre-implantation
Population: All subjects met qualification criteria of prior elevated NT-proBNP/BNP only and had successful implantation of CardioMEMS™ HF System.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP Only Group] | 0 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs Post- vs. Pre-implantation [Elevated NT-proBNP/BNP Only Group] | 0.265 events per patient-year |
Secondary
(Single Arm) HFHs Post- vs. Pre-implantation [Previous HF Hospitalization Only Group]
The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation
Time frame: 12 months post-implantation vs 12 months pre-implantation
Population: All subjects met qualification criteria of previous HF hospitalization only and had successful implantation of CardioMEMS™ HF System.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs Post- vs. Pre-implantation [Previous HF Hospitalization Only Group] | 1.170 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs Post- vs. Pre-implantation [Previous HF Hospitalization Only Group] | 0.540 events per patient-year |
p-value: <0.000195% CI: [0.39, 0.54]Anderson-Gill model (robust sandwich)
Secondary
(Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis]
The number of heart failure hospitalizations (HFHs)
Time frame: 12 Months Post Implantation
Population: The HFH event was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.175 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 1.132 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 1.660 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.269 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.510 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) HFHs [Subject Based COVID-19 Sensitivity Analysis] | 0.719 events per patient-year |
Secondary
(Single Arm) Intravenous Diuretic Visits
The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy
Time frame: 12 months post-implantation
Population: The secondary endpoint was analyzed in the endpoint-contributing populations, which consists of subjects with successful implantation in three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. Annualized event rate was estimated from the Andersen-Gill model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Intravenous Diuretic Visits | 0.027 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Intravenous Diuretic Visits | 0.077 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits | 0.123 events per patient-year |
p-value: <0.0001ANOVA
Secondary
(Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis]
The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy
Time frame: 12 Months Post Implantation
Population: The event was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization, but excluding events adjudicated as either related or possibly related to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.027 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.077 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.123 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.027 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.075 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) Intravenous Diuretic Visits [Event Based COVID-19 Sensitivity Analysis] | 0.119 events per patient-year |
Secondary
(Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis]
The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy
Time frame: Events were analyzed through March 13, 2020 for pre-COVID-19 analysis (median follow-up: 5.4 months) and from March 13, 2020 through the end of subject's follow-up for during COVID-19 analysis (median follow-up: 11.2 months).
Population: The endpoints limited to the follow-up period was analyzed in the endpoint-contributing populations, which consists of subjects with successful implantation in three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. Subjects were assessed based on their follow-up time occurring pre- or during-COVID periods using a time-varying covariate. The Arm/Group Titles represent the follow-up time period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.055 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.064 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.199 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.024 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.088 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) Intravenous Diuretic Visits [Follow-up Based COVID-19 Sensitivity Analysis] | 0.114 events per patient-year |
Secondary
(Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis]
The number of emergency department/hospital outpatient observation (ED/OP) visits for intravenous diuretic therapy
Time frame: 12 months post-implantation
Population: The event was compared between subjects in the three qualifying groups: elevated NT-proBNP/BNP only, previous HF hospitalization only or both elevated NT-proBNP/BNP and previous HF hospitalization. The Pre-COVID-19 Arms/Groups assess participants that completed study participation prior to the start of the COVID-19 pandemic, and the During COVID-19 Arms/Groups assess participants that completed study participation during the COVID-19 pandemic.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.213 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.082 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.422 events per patient-year |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.021 events per patient-year |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.080 events per patient-year |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) Intravenous Diuretic Visits [Subject Based COVID-19 Sensitivity Analysis] | 0.101 events per patient-year |
Secondary
(Single Arm) Safety: Freedom From DSRCs
Proportion of subjects with freedom from device/system related complications (DSRCs)
Time frame: 12 months post-implantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Safety: Freedom From DSRCs | 451 Participants |
| Randomized Arm - Control Group | (Single Arm) Safety: Freedom From DSRCs | 548 Participants |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Safety: Freedom From DSRCs | 342 Participants |
Other Pre-specified
(Randomized Arm) All-cause Hospitalizations
The number of hospitalizations of any cause
Time frame: 12 months post-implantation
Population: The number of all-cause hospitalizations were analyzed in the endpoint-contributing population, which included subjects of NYHA class II/III/IV with successful implantation and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) All-cause Hospitalizations | 0.918 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) All-cause Hospitalizations | 0.973 events per patient-year |
Other Pre-specified
(Randomized Arm) BNP
Change in BNP measurements from baseline
Time frame: 12 months post-implantation
Population: Subjects that have a baseline value and at least one value at 12-month visits were analyzed. The Least Square Means (LSM) difference in BNP levels at 12 months from baseline in both Treatment and Control groups during the overall follow-up period were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) BNP | -80.61 pg/mL | Standard Error 53.17 |
| Randomized Arm - Control Group | (Randomized Arm) BNP | -20.82 pg/mL | Standard Error 55.51 |
Comparison: Comparisons of change from baseline in BNP levels at 12 months between Treatment vs Control groupp-value: 0.437395% CI: [-91.44, 211.01]Mixed Models Analysis
Other Pre-specified
(Randomized Arm) BNP
Change in BNP measurements from baseline
Time frame: 6 months post-implantation
Population: Subjects that have a baseline value and at least one value at 6-month visit were analyzed. The Least Square Means (LSM) difference in BNP levels at 6 months from baseline in both Treatment and Control groups during the overall follow-up period were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) BNP | -72.16 pg/mL | Standard Error 52.46 |
| Randomized Arm - Control Group | (Randomized Arm) BNP | -34.96 pg/mL | Standard Error 54.33 |
Comparison: Comparisons of change from baseline in BNP levels at 6 months between Treatment vs Control groupp-value: 0.622795% CI: [-111.38, 185.77]Mixed Models Analysis
Other Pre-specified
(Randomized Arm) Cardiovascular Mortality
The number of deaths with cardiovascular cause
Time frame: 12 months post-implantation
Population: The number of deaths that were cardiovascular in nature were analyzed in the endpoint contributing population, which includes subjects of NYHA class II/III/IV with successful implantation and randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Cardiovascular Mortality | 0.071 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) Cardiovascular Mortality | 0.057 events per patient-year |
Other Pre-specified
(Randomized Arm) Frequency of Subject PA Pressure Uploads
The frequency of subject uploads of PA pressure
Time frame: 12 months post-implantation
Population: Subjects with at least one eligible day during the analysis period are included in the analysis. The daily compliance (percentage of eligible days in which a subject had a reading) and weekly compliance (percentage of weeks in which a subject had at least one reading) per subject were analyzed in the endpoint contributing population that had at least one reading post-discharge from the implantation. Days when subjects did not have any reading taken during the eligible days are counted as zeroes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) Frequency of Subject PA Pressure Uploads | Daily compliance | 80.7 Percentage | Standard Error 20.4 |
| Randomized Arm - Treatment Group | (Randomized Arm) Frequency of Subject PA Pressure Uploads | Weekly compliance | 95.1 Percentage | Standard Error 13.7 |
| Randomized Arm - Control Group | (Randomized Arm) Frequency of Subject PA Pressure Uploads | Daily compliance | 73.8 Percentage | Standard Error 27 |
| Randomized Arm - Control Group | (Randomized Arm) Frequency of Subject PA Pressure Uploads | Weekly compliance | 89.1 Percentage | Standard Error 21.7 |
Other Pre-specified
(Randomized Arm) HFHs Post- vs. Pre-implantation [Control Group]
The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation
Time frame: 12 months post-implantation vs 12 months pre-implantation
Population: A comparison of HF hospitalizations in the 12 months prior to implantation compared to 12 months post implantation for the endpoint contributing population, which includes subjects of NYHA class II/III/IV with successful implantation and randomized into the Control group were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HFHs Post- vs. Pre-implantation [Control Group] | 0.710 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) HFHs Post- vs. Pre-implantation [Control Group] | 0.483 events per patient-year |
p-value: <0.000195% CI: [0.57, 0.81]Anderson-Gill model (robust sandwich)
Other Pre-specified
(Randomized Arm) HFHs Post- vs. Pre-implantation [Treatment Group]
The number of HFHs at 12 months post-implantation compared to the number of HFHs in the 12 months prior to implantation in the Treatment group
Time frame: 12 months post-implantation vs 12 months pre-implantation
Population: A comparison of HF hospitalizations in the 12 months prior to implantation compared to 12 months post implantation for the endpoint contributing population, which includes subjects of NYHA class II/III/IV with successful implantation and randomized into the Treatment group were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HFHs Post- vs. Pre-implantation [Treatment Group] | 0.643 events per patient-year |
| Randomized Arm - Control Group | (Randomized Arm) HFHs Post- vs. Pre-implantation [Treatment Group] | 0.415 events per patient-year |
p-value: <0.000195% CI: [0.53, 0.78]Anderson-Gill model (robust sandwich)
Other Pre-specified
(Randomized Arm) HF Medication Changes
The number of changes in HF medications
Time frame: 12 months post-implantation
Population: Within the endpoint-contributing population, which included subjects of NYHA class II/II/IV with successful implantation and randomized into Treatment and Control group, the number of subjects with medication changes and the number of medications changes were recorded by different classes of HF medications.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Calcium Channel Blockers | 77 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Angiotensin Receptor-Neprilysin Inhibitor (ARNi) | 194 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Beta Blockers | 370 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Aldosterone Antagonists | 323 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Digoxin | 24 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Sinus Node If Channel Inhibitors | 12 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Angiotensin-Converting Enzyme (ACE) Inhibitors | 109 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Angiotensin Receptor Blocker (ARB) | 94 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Diuretics | 3961 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Nitrates | 169 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | Vasodilators | 146 Number of medication changes |
| Randomized Arm - Treatment Group | (Randomized Arm) HF Medication Changes | SGLT2 Inhibitor | 9 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Nitrates | 101 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Angiotensin-Converting Enzyme (ACE) Inhibitors | 76 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Angiotensin Receptor-Neprilysin Inhibitor (ARNi) | 120 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | SGLT2 Inhibitor | 6 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Beta Blockers | 339 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Vasodilators | 83 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Aldosterone Antagonists | 190 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Calcium Channel Blockers | 65 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Diuretics | 2064 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Digoxin | 36 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Angiotensin Receptor Blocker (ARB) | 80 Number of medication changes |
| Randomized Arm - Control Group | (Randomized Arm) HF Medication Changes | Sinus Node If Channel Inhibitors | 4 Number of medication changes |
Other Pre-specified
(Randomized Arm) NT-proBNP
Change in NT-proBNP measurements from baseline
Time frame: 6 months post-implantation
Population: Subjects that have a baseline value and at least one value at 6-month visit were analyzed. The Least Square Means (LSM) difference in NT-proBNP levels at 6 months from baseline in both Treatment and Control groups during the overall follow-up period were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) NT-proBNP | -169.94 pg/mL | Standard Error 183.37 |
| Randomized Arm - Control Group | (Randomized Arm) NT-proBNP | 298.16 pg/mL | Standard Error 179.58 |
Comparison: Comparisons of change from baseline in NT-proBNP levels at 6months between Treatment vs Control groupp-value: 0.069295% CI: [-37.09, 973.3]Mixed Models Analysis
Other Pre-specified
(Randomized Arm) NT-proBNP
Change in NT-proBNP measurements from baseline
Time frame: 12 months post-implantation
Population: Subjects that have a baseline value and at least one value at 12-month visit were analyzed. The Least Square Means (LSM) difference in NT-proBNP levels at 12 months from baseline in both Treatment and Control groups during the overall follow-up period were analyzed using a mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) NT-proBNP | 217.23 pg/mL | Standard Error 190.28 |
| Randomized Arm - Control Group | (Randomized Arm) NT-proBNP | 501.90 pg/mL | Standard Error 189.74 |
Comparison: Comparisons of change from baseline in NT-proBNP levels at 12 months between Treatment vs Control groupp-value: 0.290395% CI: [-244.27, 813.6]Mixed Models Analysis
Other Pre-specified
(Randomized Arm) PA Pressure Measurements [AUC Analysis]
Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using an area under the curve (AUC) analysis of change from baseline on all PA pressure readings through 12 months.
Time frame: Baseline through 12 months post-implantation
Population: The PA pressure measurements were analyzed in the endpoint contributing population that had at least one reading post-discharge from the implantation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) PA Pressure Measurements [AUC Analysis] | PA Systolic Pressure | -945.0 mmHg*Days | Standard Deviation 2328.9 |
| Randomized Arm - Treatment Group | (Randomized Arm) PA Pressure Measurements [AUC Analysis] | PA Diastolic pressure | -690.5 mmHg*Days | Standard Deviation 1405.1 |
| Randomized Arm - Treatment Group | (Randomized Arm) PA Pressure Measurements [AUC Analysis] | PA Mean Pressure | -792.7 mmHg*Days | Standard Deviation 1767 |
| Randomized Arm - Control Group | (Randomized Arm) PA Pressure Measurements [AUC Analysis] | PA Systolic Pressure | -621.2 mmHg*Days | Standard Deviation 2242.3 |
| Randomized Arm - Control Group | (Randomized Arm) PA Pressure Measurements [AUC Analysis] | PA Diastolic pressure | -566.1 mmHg*Days | Standard Deviation 1360.6 |
| Randomized Arm - Control Group | (Randomized Arm) PA Pressure Measurements [AUC Analysis] | PA Mean Pressure | -582.9 mmHg*Days | Standard Deviation 1698.1 |
Comparison: Comparison of PA Systolic Pressure AUC between Treatment and Control group.p-value: 0.0214t-test, 2 sided
Comparison: Comparison of PA Diastolic Pressure AUC between Treatment and Control group.p-value: 0.1002t-test, 2 sided
Comparison: Comparison of PA Mean Pressure AUC between Treatment and Control group.p-value: 0.0402t-test, 2 sided
Other Pre-specified
(Randomized Arm) PA Pressure Measurements [Mixed Model Analysis]
Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using a mixed linear model at fixed time points (Baseline, 6 months, and 12 months) producing least-squares means.
Time frame: Baseline through 12 months post-implantation
Population: Subjects that have a baseline value and at least one value at either 6- or 12-month visits were analyzed. The Least Square Means (LSM) difference in PA pressure measurements at 6 months and 12 months from baseline in both Treatment and Control groups during the overall follow-up period were analyzed using a mixed model analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Systolic Pressure | -3.41 mmHg | Standard Error 0.44 |
| Randomized Arm - Treatment Group | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Mean Pressure | -2.90 mmHg | Standard Error 0.34 |
| Randomized Arm - Treatment Group | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Diastolic pressure | -2.52 mmHg | Standard Error 0.27 |
| Randomized Arm - Control Group | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Mean Pressure | -1.77 mmHg | Standard Error 0.35 |
| Randomized Arm - Control Group | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Diastolic pressure | -1.73 mmHg | Standard Error 0.28 |
| Randomized Arm - Control Group | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Systolic Pressure | -1.87 mmHg | Standard Error 0.46 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Systolic Pressure | -3.33 mmHg | Standard Error 0.46 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Diastolic pressure | -2.49 mmHg | Standard Error 0.28 |
| Randomized Arm - Treatment Group [During COVID-19] | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Mean Pressure | -2.80 mmHg | Standard Error 0.35 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Systolic Pressure | -2.70 mmHg | Standard Error 0.47 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Diastolic pressure | -2.29 mmHg | Standard Error 0.29 |
| Randomized Arm - Control Group [During COVID-19] | (Randomized Arm) PA Pressure Measurements [Mixed Model Analysis] | PA Mean Pressure | -2.40 mmHg | Standard Error 0.36 |
Comparison: Comparisons of PA Systolic Pressure at 6 months between Treatment vs Control groupp-value: 0.01695% CI: [0.29, 2.78]Mixed Models Analysis
Comparison: Comparisons of PA Diastolic Pressure at 6 months between Treatment vs Control group.p-value: 0.042795% CI: [0.03, 1.56]Mixed Models Analysis
Comparison: Comparisons of PA Mean Pressure at 6 months between Treatment vs Control group.p-value: 0.018895% CI: [0.19, 2.08]Mixed Models Analysis
Comparison: Comparisons of PA Systolic Pressure at 12 months between Treatment vs Control group.p-value: 0.340595% CI: [-0.66, 1.92]Mixed Models Analysis
Comparison: Comparisons of PA Diastolic Pressure at 12 months between Treatment vs Control group.p-value: 0.617495% CI: [-0.59, 0.99]Mixed Models Analysis
Comparison: Comparisons of PA Mean Pressure at 12 months between Treatment vs Control group.p-value: 0.423195% CI: [-0.58, 1.38]Mixed Models Analysis
Other Pre-specified
(Single Arm) 6MHW Test [Mixed Model Analysis]
6MHW Test Distance
Time frame: 12 months post-implantation
Population: The 6MHW distance at 12 months from baseline in each qualification criteria group were compared using mixed model analysis. Subjects who were unable to walk due to heart failure symptoms were assigned zero meters.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) 6MHW Test [Mixed Model Analysis] | -3.80 meters, m | Standard Error 5.9 |
| Randomized Arm - Control Group | (Single Arm) 6MHW Test [Mixed Model Analysis] | -5.56 meters, m | Standard Error 5.99 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) 6MHW Test [Mixed Model Analysis] | 20.18 meters, m | Standard Error 7.67 |
Other Pre-specified
(Single Arm) 6MHW Test [Mixed Model Analysis]
6MHW Test Distance
Time frame: 6 months post-implantation
Population: The 6MHW distance at 6 months from baseline in each qualification criteria group were compared using mixed model analysis. Subjects who were unable to walk due to heart failure symptoms were assigned zero meters.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) 6MHW Test [Mixed Model Analysis] | 5.25 meters, m | Standard Error 5.4 |
| Randomized Arm - Control Group | (Single Arm) 6MHW Test [Mixed Model Analysis] | 0.67 meters, m | Standard Error 5.13 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) 6MHW Test [Mixed Model Analysis] | 20.11 meters, m | Standard Error 6.62 |
Other Pre-specified
(Single Arm) All-cause Hospitalizations
The number of hospitalizations of any cause
Time frame: 12 months post-implantation
Population: All-cause hospitalizations (overnight hospitalizations for any reason, including HF) were analyzed in all three qualification criteria groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) All-cause Hospitalizations | 0.80 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) All-cause Hospitalizations | 1.216 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) All-cause Hospitalizations | 1.503 events per patient-year |
Other Pre-specified
(Single Arm) Cardiovascular Mortality
The number of deaths of cardiovascular cause
Time frame: 12 months post-implantation
Population: The number of deaths that were cardiovascular in nature were analyzed in all three qualification criteria groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Cardiovascular Mortality | 0.073 events per patient-year |
| Randomized Arm - Control Group | (Single Arm) Cardiovascular Mortality | 0.090 events per patient-year |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Cardiovascular Mortality | 0.163 events per patient-year |
Other Pre-specified
(Single Arm) EQ-5D-5L [Mixed Model Analysis]
Health status as assessed by the EQ-5D-5L Questionnaire. The data represents the EQ Visual Analogue Scale (VAS) subscale. The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score for represents a better quality of life.
Time frame: 12 months post-implantation
Population: The EQ-5D-5L scores at 12-month visit from baseline for each qualification criteria group were compared using Mixed Model Analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 3.42 scores on a scale | Standard Error 0.94 |
| Randomized Arm - Control Group | (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 0.83 scores on a scale | Standard Error 0.88 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 4.93 scores on a scale | Standard Error 1.16 |
Other Pre-specified
(Single Arm) EQ-5D-5L [Mixed Model Analysis]
Health status as assessed by the EQ-5D-5L Questionnaire. The data represents the EQ Visual Analogue Scale (VAS) subscale. The VAS records the subject's self-rated health status which ranges from a score of 0 (worst health you can imagine) to 100 (best health you can imagine). A higher VAS score for represents a better quality of life.
Time frame: 6 months post-implantation
Population: The EQ-5D-5L scores at 6-month visit from baseline for each qualification criteria group were compared using Mixed Model Analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 3.86 scores on a scale | Standard Error 0.91 |
| Randomized Arm - Control Group | (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 3.05 scores on a scale | Standard Error 0.83 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) EQ-5D-5L [Mixed Model Analysis] | 2.41 scores on a scale | Standard Error 1.09 |
Other Pre-specified
(Single Arm) Frequency of Subject PA Pressure Uploads - Daily Compliance
The frequency of subject uploads of PA pressure
Time frame: 12 months post-implantation
Population: Subjects with at least one eligible day during the analysis period are included in the analysis. The daily compliance (percentage of eligible days in which a subject had a reading) per subject were analyzed in the endpoint contributing population that had at least one reading post-discharge from the implantation. Days when subjects did not have any reading taken during the eligible days are counted as zeroes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Frequency of Subject PA Pressure Uploads - Daily Compliance | 79 Percentage | Standard Deviation 22 |
| Randomized Arm - Control Group | (Single Arm) Frequency of Subject PA Pressure Uploads - Daily Compliance | 72 Percentage | Standard Deviation 27 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Frequency of Subject PA Pressure Uploads - Daily Compliance | 74 Percentage | Standard Deviation 25 |
Other Pre-specified
(Single Arm) Frequency of Subject PA Pressure Uploads - Weekly Compliance
The frequency of subject uploads of PA pressure
Time frame: 12 months post-implantation
Population: Subjects with at least one eligible day during the analysis period are included in the analysis. The weekly compliance (percentage of weeks in which a subject had at least one reading) per subject were analyzed in the endpoint contributing population that had at least one reading post-discharge from the implantation. A week is considered eligible if the subject was eligible for readings three or more days during that week.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) Frequency of Subject PA Pressure Uploads - Weekly Compliance | 0.94 Percentage | Standard Deviation 0.14 |
| Randomized Arm - Control Group | (Single Arm) Frequency of Subject PA Pressure Uploads - Weekly Compliance | 0.90 Percentage | Standard Deviation 0.2 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) Frequency of Subject PA Pressure Uploads - Weekly Compliance | 0.91 Percentage | Standard Deviation 0.17 |
Other Pre-specified
(Single Arm) HF Medication Changes
The number of changes in HF medications
Time frame: 12 months post-implantation
Population: The number of subjects with medication changes and the total number of medications changes are provided below for different classes of HF medications for each qualification criteria group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Digoxin | 37 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Angiotensin-Converting Enzyme (ACE) Inhibitors | 50 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Angiotensin Receptor Blocker (ARB) | 61 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Angiotensin Receptor-Neprilysin Inhibitor (ARNi) | 122 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Beta Blockers | 285 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Mineralocorticoid Receptor Antagonist | 238 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Sinus Node If Channel Inhibitors | 2 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | SGLT2 Inhibitor | 73 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Nitrates | 68 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Hydralazine/Other Vasodilators | 93 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Calcium Channel Blockers | 48 Number of events |
| Randomized Arm - Treatment Group | (Single Arm) HF Medication Changes | Diuretics | 3026 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | SGLT2 Inhibitor | 66 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Diuretics | 4573 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Hydralazine/Other Vasodilators | 121 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Sinus Node If Channel Inhibitors | 3 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Angiotensin-Converting Enzyme (ACE) Inhibitors | 69 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Calcium Channel Blockers | 82 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Mineralocorticoid Receptor Antagonist | 409 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Angiotensin Receptor Blocker (ARB) | 127 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Digoxin | 23 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Nitrates | 88 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Angiotensin Receptor-Neprilysin Inhibitor (ARNi) | 135 Number of events |
| Randomized Arm - Control Group | (Single Arm) HF Medication Changes | Beta Blockers | 358 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Angiotensin Receptor-Neprilysin Inhibitor (ARNi) | 98 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Beta Blockers | 239 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Digoxin | 18 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Sinus Node If Channel Inhibitors | 1 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Mineralocorticoid Receptor Antagonist | 216 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Hydralazine/Other Vasodilators | 102 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Diuretics | 2630 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | SGLT2 Inhibitor | 46 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Angiotensin-Converting Enzyme (ACE) Inhibitors | 42 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Calcium Channel Blockers | 48 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Angiotensin Receptor Blocker (ARB) | 57 Number of events |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) HF Medication Changes | Nitrates | 68 Number of events |
Other Pre-specified
(Single Arm) KCCQ-12 [Mixed Model Analysis]
Health status as assessed by the KCCQ-12 The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life on a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status.
Time frame: 6 months post-implantation
Population: The change in KCCQ-12 scores at 6 months visit from baseline in each qualification criteria group were analyzed using mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) KCCQ-12 [Mixed Model Analysis] | 6.19 scores on a scale | Standard Error 0.98 |
| Randomized Arm - Control Group | (Single Arm) KCCQ-12 [Mixed Model Analysis] | 5.47 scores on a scale | Standard Error 0.9 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) KCCQ-12 [Mixed Model Analysis] | 10.70 scores on a scale | Standard Error 1.18 |
Other Pre-specified
(Single Arm) KCCQ-12 [Mixed Model Analysis]
Health status as assessed by the KCCQ-12 The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated health-related quality of life measure for heart failure and was qualified by the FDA as a medical device development tool in 2017. The KCCQ-12 quantifies physical function, symptoms (frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life on a scale from 0 to 100. An overall summary score (OSS) is derived by averaging scores from each domain, with a higher score reflecting a better health status.
Time frame: 12 months post-implantation
Population: The change in KCCQ-12 scores at 12 months visit from baseline in each qualification criteria group were analyzed using mixed model analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) KCCQ-12 [Mixed Model Analysis] | 6.53 scores on a scale | Standard Error 1.07 |
| Randomized Arm - Control Group | (Single Arm) KCCQ-12 [Mixed Model Analysis] | 5.00 scores on a scale | Standard Error 0.99 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) KCCQ-12 [Mixed Model Analysis] | 11.85 scores on a scale | Standard Error 1.32 |
Other Pre-specified
(Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis]
Either change in N-terminal pro-brain natriuretic peptide (NT-proBNP) or Brain natriuretic peptide (BNP) measurements at 6 months visits from baseline.
Time frame: 6 months post-implantation
Population: Either BNP or NT-proBNP levels were measured at baseline, 6 months and 12 months in each qualification criteria group. Change from baseline at 6 months were analyzed using mixed model analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | BNP | 40.81 pg/mL | Standard Error 38.5 |
| Randomized Arm - Treatment Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | NT-proBNP | -55.40 pg/mL | Standard Error 153.36 |
| Randomized Arm - Control Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | BNP | -103.33 pg/mL | Standard Error 32.91 |
| Randomized Arm - Control Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | NT-proBNP | -174.83 pg/mL | Standard Error 151.97 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | BNP | -6.45 pg/mL | Standard Error 41.5 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | NT-proBNP | -102.91 pg/mL | Standard Error 194.87 |
Other Pre-specified
(Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis]
Either change in N-terminal pro-brain natriuretic peptide (NT-proBNP) or Brain natriuretic peptide (BNP) measurements at 6 months and 12 months visits from baseline.
Time frame: 12 months post-implantation
Population: Either BNP or NT-proBNP levels were measured at baseline, 6 months and 12 months in each qualification criteria group. Change from baseline at 12 months were analyzed using mixed model analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | NT-proBNP | -15.17 pg/mL | Standard Error 206.01 |
| Randomized Arm - Treatment Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | BNP | -11.23 pg/mL | Standard Error 37.73 |
| Randomized Arm - Control Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | BNP | -79.01 pg/mL | Standard Error 32.23 |
| Randomized Arm - Control Group | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | NT-proBNP | 348.49 pg/mL | Standard Error 214.19 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | BNP | -17.71 pg/mL | Standard Error 41.92 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) NT-proBNP (or BNP) [Mixed Model Analysis] | NT-proBNP | 259.33 pg/mL | Standard Error 279.57 |
Other Pre-specified
(Single Arm) PA Pressure Measurements [AUC Analysis]
Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using area under the curve (AUC) analysis of PA pressure across the full follow-up period
Time frame: Baseline through 12 months post-implantation
Population: Change in PA pressure at 6 and 12 month visits from baseline were analyzed in each qualification group using AUC analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Diastolic Pressure | -868.16 mmHg*Days | Standard Deviation 1410.07 |
| Randomized Arm - Treatment Group | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Systolic Pressure | -1033.79 mmHg*Days | Standard Deviation 2457.95 |
| Randomized Arm - Treatment Group | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Mean Pressure | -929.39 mmHg*Days | Standard Deviation 1794.2 |
| Randomized Arm - Control Group | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Diastolic Pressure | -723.29 mmHg*Days | Standard Deviation 1529.73 |
| Randomized Arm - Control Group | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Systolic Pressure | -1021.13 mmHg*Days | Standard Deviation 2374.17 |
| Randomized Arm - Control Group | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Mean Pressure | -832.21 mmHg*Days | Standard Deviation 1832.2 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Systolic Pressure | -1179.42 mmHg*Days | Standard Deviation 2588.9 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Mean Pressure | -973.97 mmHg*Days | Standard Deviation 1904.05 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) PA Pressure Measurements [AUC Analysis] | PA Diastolic Pressure | -847.94 mmHg*Days | Standard Deviation 1489.96 |
Other Pre-specified
(Single Arm) PA Pressure Measurements [Mixed Model Analysis]
Changes in PA pressure relative to baseline for systolic, diastolic, and mean PA pressures analyzed using a mixed linear model at fixed time points (Baseline, 6 months, and 12 months) producing least-squares means.
Time frame: Baseline through 12 months post-implantation
Population: Change in PA pressure at 6 and 12 month visits from baseline was analyzed in each qualification group using a mixed model analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Arm - Treatment Group | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Diastolic Pressure | -2.93 mmHg | Standard Error 0.26 |
| Randomized Arm - Treatment Group | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Mean Pressure | -3.22 mmHg | Standard Error 0.32 |
| Randomized Arm - Treatment Group | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Systolic Pressure | -3.79 mmHg | Standard Error 0.43 |
| Randomized Arm - Control Group | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Mean Pressure | -2.73 mmHg | Standard Error 0.29 |
| Randomized Arm - Control Group | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Diastolic Pressure | -2.34 mmHg | Standard Error 0.24 |
| Randomized Arm - Control Group | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Systolic Pressure | -3.32 mmHg | Standard Error 0.39 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Diastolic Pressure | -2.66 mmHg | Standard Error 0.31 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Systolic Pressure | -3.86 mmHg | Standard Error 0.52 |
| Randomized Arm - Treatment Group [During COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Mean Pressure | -3.07 mmHg | Standard Error 0.39 |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Systolic Pressure | -3.49 mmHg | Standard Error 0.49 |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Diastolic Pressure | -2.71 mmHg | Standard Error 0.29 |
| Randomized Arm - Control Group [During COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Mean Pressure | -2.92 mmHg | Standard Error 0.36 |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Diastolic Pressure | -2.57 mmHg | Standard Error 0.27 |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Systolic Pressure | -3.34 mmHg | Standard Error 0.46 |
| Randomized Arm - Treatment Group (12 Month) [Pre-COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Mean Pressure | -2.84 mmHg | Standard Error 0.34 |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Mean Pressure | -3.60 mmHg | Standard Error 0.44 |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Systolic Pressure | -4.32 mmHg | Standard Error 0.6 |
| Randomized Arm - Control Group (12 Month) [Pre-COVID-19] | (Single Arm) PA Pressure Measurements [Mixed Model Analysis] | Change in PA Diastolic Pressure | -3.17 mmHg | Standard Error 0.36 |