PROACTIVE-HF IDE Trial Heart Failure NYHA Class III

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).

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%.

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%.

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

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.

Cardiac and all-cause mortality

Intravenous (IV) diuretic visits

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

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

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.

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.

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.

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

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

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.

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

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

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

Number of combined outcome of:

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

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

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