Trial Outcomes & Findings for PROACTIVE-HF IDE Trial Heart Failure NYHA Class III (NCT NCT04089059)

Results Overview

The primary efficacy endpoint was the 6-month incidence of HF related hospitalizations or all-cause mortality in the modified Intent-to-Treat (mITT) population. As per the approved protocol/CIP, for study success the upper confidence bound of the observed event rate in the mITT population was required to be less than the performance goal (PG) of 0.43 events per patient 6-month, or equivalently, the corresponding p-value from the hypothesis test of 6-month incidence rate compared to PG was less than 0.025. Furthermore, the observed incidence rate was required to be less than 0.37. The 6-month incidence rate was derived using a Poisson regression with the number of events as the dependent variable and the exposure time as an offset term. In these analyses, a subject's exposure time was defined as the time to death, early study discontinuation, or 6 months (whichever occurred first).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

NA

Target enrollment

738 participants

Primary outcome timeframe

6 months

Results posted on

2025-03-03

Participant Flow

Enrollment was initiated on January 10, 2020, and completed on March 9, 2023, among 77 sites in the United States and five (5) sites in Ireland and Belgium. The last implant procedure was performed on March 31, 2023. The patient population consisted of male and female patients, ≥ 18 years of age with a diagnosis of NYHA Class III HF who met the study patient selection criteria.

Of the 738 enrolled subjects, 528 received an implant, 125 had screen failure and 85 were withdrawn prior to implant. Of 85 withdrawn subjects, in 37 instances the implant procedure was aborted prior to deploying the implant. Of 528 subjects implanted, 72 were in the control group (eliminated in trial redesign). The remaining 456 patients form the mITT population, which was used for all efficacy analyses. All safety analyses used the ITT population (456 mITT + 37 withdrawn = 493 patients).

Participant milestones

Participant milestones
Measure	Former Control Arm Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Former Treatment Arm Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor before and after trial redesign.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Overall Study STARTED	72	88	368
Overall Study COMPLETED	66	82	343
Overall Study NOT COMPLETED	6	6	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PROACTIVE-HF IDE Trial Heart Failure NYHA Class III

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm. Cordella™ Pulmonary Artery Sensor System: The Cordella PA Sensor System (CorPASS) is intended to measure, record, and transmit pulmonary artery pressure (PAP) data from NYHA Class III heart failure patients at home to clinicians for assessment and patient-centered heart failure management and comprises of seven subsystems that operate together to take daily Pulmonary Artery Pressure (PAP) readings at a patient's home and transmit the results to a care provider for evaluation. 1. Cordella Sensor 2. Cordella Delivery System 3. myCordella Patient Reader 4. Reader Dock 5. Cordella Calibration Equipment (CalEQ) 6. myCordella Hub 7. Cordella Data Analysis Platform (CDAP)	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Total n=528 Participants Total of all reporting groups
Age, Continuous	63.5 Years STANDARD_DEVIATION 12.53 • n=5 Participants	65.9 Years STANDARD_DEVIATION 11.26 • n=7 Participants	63.8 Years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	180 Participants n=5 Participants	30 Participants n=7 Participants	210 Participants n=5 Participants
Sex: Female, Male Male	276 Participants n=5 Participants	42 Participants n=7 Participants	318 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants	5 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	401 Participants n=5 Participants	61 Participants n=7 Participants	462 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	35 Participants n=5 Participants	6 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	84 Participants n=5 Participants	11 Participants n=7 Participants	95 Participants n=5 Participants
Race (NIH/OMB) White	347 Participants n=5 Participants	56 Participants n=7 Participants	403 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Belgium	12 participants n=5 Participants	0 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment United States	438 participants n=5 Participants	72 participants n=7 Participants	510 participants n=5 Participants
Region of Enrollment Ireland	6 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

The primary efficacy endpoint was the 6-month incidence of HF related hospitalizations or all-cause mortality in the modified Intent-to-Treat (mITT) population. As per the approved protocol/CIP, for study success the upper confidence bound of the observed event rate in the mITT population was required to be less than the performance goal (PG) of 0.43 events per patient 6-month, or equivalently, the corresponding p-value from the hypothesis test of 6-month incidence rate compared to PG was less than 0.025. Furthermore, the observed incidence rate was required to be less than 0.37. The 6-month incidence rate was derived using a Poisson regression with the number of events as the dependent variable and the exposure time as an offset term. In these analyses, a subject's exposure time was defined as the time to death, early study discontinuation, or 6 months (whichever occurred first).

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Efficacy 6 Month Incidence of HF Related Hospitalizations (HFH) or All-cause Mortality	0.2787 Events Per Patient Per 6 Months Interval 0.1798 to 0.432	0.1549 Events Per Patient Per 6 Months Interval 0.1225 to 0.1957	—	—

PRIMARY outcome

Timeframe: 6 months

Population: The Intent-to-Treat Population (ITT) includes all enrolled subjects intended to receive the Cordella PA Sensor who entered the Cath Lab, including those in whom Implant Procedure was not attempted for whatever reason (e.g., Cordella PA Sensor Implant cannot be performed due to anatomical reasons) from the Open Label Arm and Former Treatment Arm. Patients in this population in whom the Cordella PA Sensor Implant was not attempted were followed through 30 days for safety purposes.

A device/system related complication (DSRC) is defined as an AE that is, or is possibly, related to the device/system (Cordella PA Sensor or electronic components) and is either treated invasively (other than intramuscular medication or diagnostic RHC) or results in subject´s death or explant of the device. The first primary safety endpoint describes freedom from a DSRC through 6 months and was tested against the null rate of 90%.

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=493 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Safety: Freedom From Device/System Related Complication	0.986 Proportion of patients without a DSRC Interval 0.905 to 0.998	0.992 Proportion of patients without a DSRC Interval 0.979 to 0.997	—	—

PRIMARY outcome

Timeframe: 6 months

Population: The Intent-to-Treat Population (ITT) includes all enrolled subjects intended to receive the Cordella PA Sensor who entered the Cath Lab, including those in whom Implant Procedure was not attempted for whatever reason (e.g., Cordella PA Sensor Implant cannot be performed due to anatomical reasons) from the Open Label Arm and Former Treatment Arm. Patients in this population in whom the Cordella PA Sensor Implant was not attempted were followed through 30 days for safety purposes.

A pressure sensor failure (PSF) occurs when the sensor malfunctions to the point that no readings can be obtained from the sensor after all attempts are exhausted including troubleshooting the system to rule out any problems with the electronic components. The second primary safety endpoint describes freedom from Pressure Sensor Failure through 6 months, it was tested against the null rate of 95%.

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=493 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Safety: Freedom From Pressure Sensor Failure	1.000 Proportion of patients without a PSF Interval 1.0 to 1.0	0.998 Proportion of patients without a PSF Interval 0.986 to 1.0	—	—

SECONDARY outcome

Timeframe: 6 Months prior to implant and 6 months post implant

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Number of HF Hospitalizations at 6 months post-implant compared to the number of HF Hospitalizations in the 6 months prior to implant

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
HF Hospitalizations Total HF Hospitalizations events in 6 months before implant	36 events	266 events	—	—
HF Hospitalizations Total HF Hospitalizations events in 6 months after implant	18 events	60 events	—	—

SECONDARY outcome

Timeframe: 6 months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Incidence rate of HF Hospitalizations, Emergency Department/ Hospital Outpatient IV diuretic visits of Former Control Arm and Modified Intent to Treat at 6 months post implant, added together with equal weighting into a total number of events.

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits.	0.2508 Events Per Patient Per 6 Months Interval 0.158 to 0.3981	0.1703 Events Per Patient Per 6 Months Interval 0.1362 to 0.213	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Cardiac and all-cause mortality

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Mortality All-cause Mortality	2 Participants	10 Participants	—	—
Mortality Cardiac Mortality	2 Participants	6 Participants	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Intravenous (IV) diuretic visits

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
IV Diuretic Visits	0 events	17 events	—	—

SECONDARY outcome

Timeframe: 6 months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT. mPAP target was 20 mmHG, thus patients above 20 mmHG for mPAP were assigned to Above Target group and patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.

Change in PAP: a. From Baseline through 6 months in subjects with a baseline mPAP i. above target range ii. within or below target range iii. Overall

Outcome measures

Outcome measures
Measure	Former Control Arm n=197 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=437 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline n=240 Participants mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Pulmonary Artery Pressure (PAP) Baseline	29.2 mmHG of mPAP Standard Deviation 7.7	20.2 mmHG of mPAP Standard Deviation 10.3	12.8 mmHG of mPAP Standard Deviation 4.9	—
Pulmonary Artery Pressure (PAP) 6 Months	26.8 mmHG of mPAP Standard Deviation 9.2	21.4 mmHG of mPAP Standard Deviation 9.3	17.0 mmHG of mPAP Standard Deviation 6.8	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Proportion of device success as documented by ability of the System to successfully transmit PAP data transmit PAP data

Outcome measures

Outcome measures
Measure	Former Control Arm Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Device Success	—	0.991 Proportion of device readings successful	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: All primary and secondary effectiveness analyses are performed on the Modified Intent-to-Treat Population (mITT). For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of patients in these results than in the mITT population overall.

The Quality of Life KCCQ questionnaire is a measure of health-related quality of life. It is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life related to Heart Failure. From 23-items, the Overall Summary Score (OSS) will be calculated. In the OSS, each of the 23 items are converted onto a 0 to 100 scale using this formula: (Raw score - Minimum Raw Score)/(Maximum Raw Score - Minimum Raw Score) \* 100. Then these are averaged across the 23 items. A score of 100 (the maximum score) would indicate maximum quality of life relating to heart failure and a score of 0 (scale minimum) would indicate the worst possible quality of life relating to heart failure, with higher scores generally indicating higher quality of life.

Outcome measures

Outcome measures
Measure	Former Control Arm n=65 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=421 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Baseline	49.7 points Standard Deviation 23.8	52.8 points Standard Deviation 22.8	—	—
Kansas City Cardiomyopathy Questionnaire (KCCQ) 6 Month	54.2 points Standard Deviation 25.2	57.8 points Standard Deviation 24.2	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: All primary and secondary effectiveness analyses are performed on the Modified Intent-to-Treat Population (mITT). For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of patients in these results than in the mITT population overall.

New York Heart Association (NYHA) Classification at 6 months. The New York Heart Association (NYHA) Classification provides a way of classifying the extent of heart failure by classifying patients in one of four categories based on their limitations during physical activity and in degree of shortness of breath and or angina pain. Class I is the least severe and Class IV is the most severe. The classes are: Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

Outcome measures

Outcome measures
Measure	Former Control Arm n=65 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=414 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
NYHA I	3 Participants	23 Participants	—	—
NYHA II	16 Participants	121 Participants	—	—
NYHA III	46 Participants	262 Participants	—	—
NYHA IV	0 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT. For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of participants in these results than in the mITT population overall.

Functional status improvement, as measured by 6-Minute Walk Test total distance walked. The 6-Minute Walk Test (6MWT) is a test that measures the total distance an individual can walk on a flat, hard surface in 6 minutes. It is commonly used to evaluate functional exercise capacity in patients with conditions including heart failure. The minimum score possible is 0, which would represent an inability to walk any distance. There is no maximum score, as a patient could theoretically walk any distance in 6 minutes though 800 meters considered the top reference range, which is what would be expected by elite athletes. Higher score indicate greater higher exercise capacity and lower scores indicate lower exercise capacity.

Outcome measures

Outcome measures
Measure	Former Control Arm n=70 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=436 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
6-Minute Walk Test 6 Months	299.4 Meters Walked Standard Deviation 147.5	283.2 Meters Walked Standard Deviation 123.9	—	—
6-Minute Walk Test Baseline	281.5 Meters Walked Standard Deviation 133.6	259.5 Meters Walked Standard Deviation 121.1	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Intent-to-Treat Population (ITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All safety analyses were performed on the ITT population.

Number and percent of patients with serious adverse events throughout the study (site-reported).

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=493 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Number and Percent of Patients With Serious Adverse Events Subjects with at least one predefined SAE	31 Participants	196 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Heart Failure	16 Participants	79 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Acute Kidney Injury (AKIN)	7 Participants	22 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Bleeding	4 Participants	6 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Myocardial Infarction (MI)	1 Participants	3 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Pulmonary Embolism	0 Participants	6 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Pulmonary Occlusion	0 Participants	0 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Stroke and Trans Ischemic Attach (TIA)	1 Participants	0 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Vascular Access Site and Access-Related Complications	2 Participants	4 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Vessel Trauma	0 Participants	4 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Other	17 Participants	123 Participants	—	—
Number and Percent of Patients With Serious Adverse Events ED Visit	0 Participants	4 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Hospitalization	16 Participants	72 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Urgent, Unscheduled Outpatient Office/ Practice	0 Participants	2 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Conduction Disturbances and Arrhythmias	4 Participants	28 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Hemoptysis	1 Participants	12 Participants	—	—
Number and Percent of Patients With Serious Adverse Events Renal Dysfunction	1 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Participants who received Cordella PA sensor implant.

Incidence of HF Hospitalizations or all-cause mortality at 12 months calculated from Poisson regression.

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Incidence of HF Hospitalizations or All-cause Mortality	0.5438 Events Per Patient Per 12 Months Interval 0.3957 to 0.7474	0.3629 Events Per Patient Per 12 Months Interval 0.3107 to 0.4239	—	—

SECONDARY outcome

Timeframe: 6 months

Population: All primary and secondary effectiveness analyses are performed on the Modified Intent-to-Treat Population (mITT). For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of patients in these results than in the mITT population overall.

Change of N-terminal pro B-type Natriuretic Peptide (NT-proBNP) from Baseline through 6 months. NT-proBNP is a biomarker used to assess heart failure (HF). NT-proBNP levels vary widely and are reported in picograms per milliliter (pg/mL) or nanograms per liter (ng/L), with no predefined maximum value. Zero is a hypothetical minimum value though this is, in practice, not possible. In the current context, higher scores indicate more severe heart failure and lower levels indicate less severe heart failure.

Outcome measures

Outcome measures
Measure	Former Control Arm n=70 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=447 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Baseline	1786.8 pg/ml Standard Deviation 3809.4	1731.4 pg/ml Standard Deviation 3012.8	—	—
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) 6 Months	1345.6 pg/ml Standard Deviation 2435.7	1632.5 pg/ml Standard Deviation 2742.4	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Days Alive and Out of Hospital (DAOH) during the 6 months after implant

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Days Alive and Out of Hospital (DAOH)	173.7 days Standard Deviation 19.6	172.0 days Standard Deviation 27.2	—	—

SECONDARY outcome

Timeframe: 6 Months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Number of patients (%) with heart failure related medication changes in the 6 months after implant

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Number of Heart Failure Related Medication Changes 1 Month to 3 Months	25 Participants	227 Participants	—	—
Number of Heart Failure Related Medication Changes 3 Months to 6 Months	32 Participants	260 Participants	—	—
Number of Heart Failure Related Medication Changes Baseline to 1 Month	25 Participants	234 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Participants who received the Cordella PA sensor implant.

Number of HF Hospitalizations or all-cause mortality at 12 months

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Number of HF Hospitalization or All-cause Mortality Heart Failure Hospitilizations	33 Events	126 Events	—	—
Number of HF Hospitalization or All-cause Mortality All-Cause Deaths	5 Events	33 Events	—	—

SECONDARY outcome

Timeframe: 6 months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Number of combined outcome of: 1. First and recurrent Heart Failure Hospitalizations 2. Emergency Department / Hospital Outpatient IV diuretic visits all-cause mortality at 6 months, added together with equal weighting into a total number of events.

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline n=88 Participants mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm n=368 Participants Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality	20 events	87 events	17 events	70 events

SECONDARY outcome

Timeframe: 6 months

Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.

Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits at 6 months.

Outcome measures

Outcome measures
Measure	Former Control Arm n=72 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=456 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline n=88 Participants mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm n=268 Participants Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits	18 Events	77 Events	15 Events	62 Events

SECONDARY outcome

Timeframe: 6 months

Population: The Intent-to-Treat Population (ITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All safety analyses were performed on the ITT population.

Frequency of implant procedure and procedure related adverse events and serious adverse events

Outcome measures

Outcome measures
Measure	Former Control Arm Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.	Modified Intent-to-Treat (mITT) n=493 Participants Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.	Within/BelowTarget mPAP at Baseline mPAP target was 20 mmHG, thus patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.	Open Label Arm Recruited after trial redesign. Received standard of care HF management using the Cordella Heart Failure System (CHFS) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor.
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Subjects with at least one predefined AE or SAE with study device or implant procedure relationship	—	36 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Bleeding	—	3 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Conduction Disturbances and Arrhythmias	—	4 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Heart Failure	—	2 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Hemoptysis	—	14 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Pulmonary Embolism	—	1 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Vascular Access Site and Access-Related Complications	—	12 Participants	—	—
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events Other	—	16 Participants	—	—

Adverse Events

Intent-to-Treat (ITT)

Serious events: 278 serious events

Other events: 379 other events

Deaths: 33 deaths

Former Control Arm

Serious events: 47 serious events

Other events: 60 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Liviu Klein

UCSF School of Medicine

Phone: 415-476-2143

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Intent-to-Treat (ITT) n=493 participants at risk Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor OR withdrew from trial and did not receive an implant. To capture safety of all patients in the trial, the ITT sample was used in all safety analyses. In contrast, the mITT sample was used in all efficacy analyses as, as only mITT patients received the active treatment. See participant flow section for more details. Cordella™ Pulmonary Artery Sensor System: The Cordella PA Sensor System (CorPASS) is intended to measure, record, and transmit pulmonary artery pressure (PAP) data from NYHA Class III heart failure patients at home to clinicians for assessment and patient-centered heart failure management and comprises of seven subsystems that operate together to take daily Pulmonary Artery Pressure (PAP) readings at a patient's home and transmit the results to a care provider for evaluation. 1. Cordella Sensor 2. Cordella Delivery System 3. myCordella Patient Reader 4. Reader Dock 5. Cordella Calibration Equipment (CalEQ) 6. myCordella Hub 7. Cordella Data Analysis Platform (CDAP)	Former Control Arm n=72 participants at risk Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor.
Cardiac disorders Heart Failure	26.8% 132/493 • Number of events 193 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	31.9% 23/72 • Number of events 58 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Surgical and medical procedures Emergency Department Visit	1.2% 6/493 • Number of events 6 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	0.00% 0/72 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Surgical and medical procedures Hospitalization	24.7% 122/493 • Number of events 177 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	31.9% 23/72 • Number of events 58 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Surgical and medical procedures Urgent, Unscheduled Outpatient Office/ Practice	0.41% 2/493 • Number of events 2 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	0.00% 0/72 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Renal and urinary disorders Acute Kidney Injury	8.3% 41/493 • Number of events 55 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	11.1% 8/72 • Number of events 11 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Blood and lymphatic system disorders Bleeding	2.4% 12/493 • Number of events 13 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	6.9% 5/72 • Number of events 5 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Cardiac disorders Conduction Disturbances and Arrhythmias	9.7% 48/493 • Number of events 66 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	13.9% 10/72 • Number of events 10 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Respiratory, thoracic and mediastinal disorders Hemoptysis	2.4% 12/493 • Number of events 14 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	1.4% 1/72 • Number of events 1 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Cardiac disorders Myocardial Infarction	1.2% 6/493 • Number of events 6 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	1.4% 1/72 • Number of events 1 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	1.2% 6/493 • Number of events 7 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	1.4% 1/72 • Number of events 1 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Respiratory, thoracic and mediastinal disorders Pulmonary Occlusion	0.00% 0/493 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	0.00% 0/72 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Renal and urinary disorders Renal Dysfunction	2.4% 12/493 • Number of events 15 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	4.2% 3/72 • Number of events 3 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Cardiac disorders Stroke and Trans Ischemic Attack	0.41% 2/493 • Number of events 2 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	2.8% 2/72 • Number of events 2 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Cardiac disorders Vascular Access Site and Access-Related Complications	0.81% 4/493 • Number of events 4 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	2.8% 2/72 • Number of events 2 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
Cardiac disorders Vessel Trauma	0.81% 4/493 • Number of events 4 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	0.00% 0/72 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.
General disorders Other	37.5% 185/493 • Number of events 404 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.	33.3% 24/72 • Number of events 61 • 12 months The event is an SAE when the patient outcome is: * Death * Life-threatening * Hospitalization (initial or prolonged) * Disability or permanent change * Congenital Anomaly/Birth Defect * Required Intervention to Prevent Permanent Impairment or Damage * Other Serious (Important Medical Events) A planned hospitalization for a pre-existing condition, or a procedure required by the protocol, without a serious deterioration in health, is not considered to be a serious adverse event.