Safety and feasibility of hemodynamic pulmonary artery pressure monitoring using the CardioMEMS device in LVAD management

Abstract Background There is a clinical need for additional remote tools to improve left ventricular assist device (LVAD) patient management. The aim of this pilot concept study was to assess the safety and feasibility of optimizing patient management with add‐on remote hemodynamic monitoring using the CardioMEMS in LVAD patients during different treatment stages. Methods Ten consecutive patients accepted and clinically ready for (semi‐) elective HeartMate 3 LVAD surgery were included. All patients received a CardioMEMS to optimize filling pressure before surgery. Patients were categorized into those with normal mean pulmonary artery pressure (mPAP) (≤25 mmHg, n = 4) or elevated mPAP (>25 mmHg, n = 6), and compared to a historical cohort (n = 20). Endpoints were CardioMEMS device safety and a combined endpoint of all‐cause mortality, acute kidney injury, renal replacement therapy and/or right ventricular failure at 1‐year follow‐up. Additionally, we investigated hospital‐free survival and improvement in quality of life (QoL) and exercise tolerance. Results No safety issues or signal interferences were observed. The combined endpoint occurred in 60% of historical controls, 0% in normal and 83% in elevated mPAP group. Post‐discharge, the hospital‐free survival was significantly better, and the QoL improved more in the normal compared to the elevated mPAP group. Conclusion Remote hemodynamic monitoring in LVAD patients is safe and feasible with the CardioMEMS, which could be used to identify patients at elevated risk of complications as well as optimize patient management remotely during the out‐patient phase with less frequent hospitalizations. Larger pivotal studies are warranted to test the hypothesis generated from this concept study.


| INTRODUCTION
Left ventricular assists device (LVAD) therapy is a rapidly growing treatment option for end-stage heart failure (HF) patients refractory to medical treatment. 1 Due to technological improvements and increasing experience with LVAD therapy, the overall survival of LVAD patients has significantly improved since the early 2000s. 2 Despite these improvements, early and late LVAD-related complications, such as right ventricular (RV) failure, acute kidney injury (AKI), LVAD-related infections and major gastro-intestinal bleedings, are still frequent. [3][4][5] Rehospitalization and complication rates in the out-patient phase of LVAD patients remain very high. 6 There is a great clinical need for physicians treating LVAD patients to have additional tools to monitor patient management, especially remotely outside the hospital. Currently, no remote monitoring tools are used in LVAD care, except physical signs, such as weight and rhythm.
LVAD management is mostly guided by signs and symptoms during the physical examination, and incidental monitoring of the static pump measurements provided by the LVAD during out-patient visits. 7 Recently, remote hemodynamic monitoring using the Cardi-oMEMS device (Abbott Inc.) is safe and effective in chronic HF patients. 8 A new concept is to use the CardioMEMS device as a hybrid with the LVAD device, which has not been performed worldwide in a prospective manner.
We hypothesized that the additional hemodynamic data provided by CardioMEMS could aid physicians involved in LVAD management in three stages of treatment: Pre-LVAD surgery, the hemodynamic feedback can be used to optimize patients towards surgery by decongesting the kidney and RV. Thereby, the risk of renal or RV failure can be reduced, or if elevated pulmonary artery pressure (PAP) remains one can take additional measures to timely support for the RV with higher inotropes or temporary assist devices for the RV and/or early start of dialysis.
At the intensive care unit (ICU), noninvasive hemodynamic feedback could aid in optimizing fluid state (potentially restrict the fluid overload during the first days post-LVAD surgery, which strains the RV) as well as to optimize pump settings on top of echocardiography. While some can argue this phase could be managed by the regular Swan-Ganz catheter, one is more at risk for complications, such as bleeding, pneumothorax, rhythm disturbances and infections.
CardioMEMS can also prove its potential after discharge from the ICU to the regular ward and out-patient clinic to individualize patient care, including fluid state, and potentially reduce the number of hospitalizations, early discovery of LVAD-related complications and improve quality of life. Therefore, we set up a pilot concept study to test this hypothesis for assessing the safety and feasibility of using CardioMEMS in the preoperative period as well as the ICU and out-patient phase in LVAD patients. 9 If proven feasible and clinically useful, these findings will be very clinically relevant to further study in larger pivotal studies to improve LVAD patient management.

| MATERIALS AND METHODS
A detailed description of the design and methods of the HEMO-VAD pilot study has been published previously. 9 In brief, ten consecutive chronic HF patients with New-York Heart Association functional

| CardioMEMS cohort
The ten enrolled patients received a CardioMEMS device at baseline, within one day of enrollment at the heart team decision when the patient was accepted for LVAD and deemed clinically ready for surgery (normally would have proceeded towards surgery directly).
During a right heart catheterization, the CardioMEMS device is implanted, using access via the femoral vein. Pulmonary arteriogram is used to identify an appropriate target vessel, based on the vessel size and location. When the target vessel is identified, the CardioMEMS delivery system is inserted over a guidewire, and advanced to the target location, where the CardioMEMS device is released. After implantation, a Swan Ganz catheter is used to calibrated the Cardi- Post-LVAD surgery, the CardioMEMS device was used to monitor the hemodynamic status of the patients at the ICU, clinical ward, and out-patient (at home). During this period, the central aim was to normalize and/or to maintain a normal mean PAP (mPAP) (≤25 mmHg), if possible, by optimizing HF treatment and pump settings.

| Safety endpoints
The endpoints of the safety analysis were freedom of sensor failures at 1-year, freedom of device-related complications at 1-year, and the freedom of signal malfunction or interference with the CardioMEMS device and HM3.

| Clinical endpoints
The primary endpoint of this analysis was the outcome 1-year post-LVAD surgery, assessed as a composite of all-cause mortality, AKI, and/or the need for renal replacement therapy (RRT), and/or RVfailure. Secondary endpoints were all-cause mortality, AKI and/or RRT, RV-failure, as well as all-cause hospitalization, changes of mPAP post-LVAD surgery, the number of medication changes post-LVAD surgery, and changes in quality of life (assessed using the EQ-5D-5L, Kansas City cardiomyopathy questionnaire and patient health questionnaire-9 (PHQ-9) questionnaires) and functional performance defined as 6-min walking distance during 1-year of out-patient remote management of LVAD patients with CardioMEMS.
AKI was defined as a minimum 1.5 times increase of baseline serum creatinine during the first seven days post-LVAD implantation, according to the kidney disease improving global outcome criteria. 10 RV-failure was defined as the need of continuous inotropic support for ≥14 days, (temporary) right ventricular assist device support or nitric oxide ventilation for ≥48 h. 11

| RESULTS
In total, 30 patients were included in this analysis, ten patients in the CardioMEMS cohort, and 20 patients in the historical cohort. The baseline characteristics of these 30 patients are shown in Table 1.

| Safety
There were no sensor failures, device-related complications, or signal malfunctions at 1-year of follow-up.

| Clinical endpoints at 1-year follow-up
The combined endpoint (consisted of all-cause mortality, AKI and/or the need for RRT, and/or RV-failure) occurred in 50.0% of the total VEENIS ET AL. in the elevated mPAP groups (p = .017, Figure 2C). RV failure occurred in 60.0% in the total CardioMEMS groups, of which 0% in the normalized mPAP group and 66.7% in the elevated mPAP groups (p = .054, Figure 2D). In the historical cohort, survival was 79.4%, AKI/RRT occurred in 35%, and RV-failure in 35.8%.

| Hospitalization-free survival at 1-year follow-up
The all-cause hospitalization-free survival (at 1 year) of the cohorts is shown in Figure 3.  Figure S1).

| COMMENT
The results from this pilot concept study demonstrate the safety and feasibility of combining PAP monitoring and HM3 management as a hybrid construction inpatient management before and after surgery as well as on the out-patient clinic. Most interestingly, the hemodynamic data identifies, with a clinically intuitive parameter, such as PAP, a high-risk group of patients with a worse outcome of LVAD surgery and more HF hospitalizations during follow-up. Likewise, patients with normal and stable pressures identify a low-risk group with good prognosis and low hospitalization rates. This is clinically

| Reducing readmissions
Although LVAD therapy improves the overall survival of end-stage HF patients, even after LVAD surgery, the hospitalization rates of these patients remain enormously high. Approximately 30% of the LVAD recipients are readmitted within 30 days after their initial discharge, 16,17 and even more than 60%-80% is at least once readmitted 1 year after their initial discharge. 18 On average, LVAD patients are admitted twice during the first year on LVAD support. 6,19 These frequent hospitalizations have a significant negative impact on the quality of life of these patients and places a large burden on hospital resources.  post-LVAD surgery, 24,25 but no further improvement after the first 6 months. 26

| LIMITATIONS
We acknowledge that patients with severe right ventricular dysfunction were excluded as well as the small sample size of our pilot study, which is hypothesis-generating, to test the safety and feasibility of a novel concept to use a PAP sensor with HM3 continuous data as a hybrid construction for the first time in a prospective study.
Intuitively, with such a clinical parameter, it makes sense to add the hemodynamic feedback to the static pump management, as it adds information to individualized management even at home. The current pilot study confirms the safety and feasibility, but the additive value will need to be tested in large scale pivotal studies.

| CONCLUSION
Remote hemodynamic monitoring in LVAD patients is safe and feasible and could be used to provide physicians involved in LVAD care at different stages with incremental information that can be used to identify patients at elevated risk of complications as well as optimize patient management remotely during the out-patient phase. The CardioMEMS sensor provides a clinically interpretable risk stratifier for adverse outcome. Larger pivotal studies are warranted to test the hypothesis generated from this pilot study on remote hemodynamic monitoring with CardioMEMS in the LVAD population.