Clinical Update of the Latest Evidence for Cardiomems Pulmonary Artery

sensors

Viewpoint Clinical Update of the Latest Evidence for CardioMEMS Pulmonary Artery Pressure Monitoring in Patients with Chronic Heart Failure: A Promising System for Remote Heart Failure Care

Jasper J. Brugts *,†, Sumant P. Radhoe †, Dilan Aydin, Dominic A. Theuns and Jesse F. Veenis

Thorax Center, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands; [email protected] (S.P.R.); [email protected] (D.A.); [email protected] (D.A.T.); [email protected] (J.F.V.) * Correspondence: [email protected] † These authors contributed equally to this work.

Abstract: The CardioMEMS pulmonary artery (PA) monitoring system placed in the left lower lobe pulmonary artery is capable of measuring pulmonary artery pressure remotely as a surrogate of intracardiac filling pressures and volume status. The technique is safe and reliable. By using remote PA monitoring for proactive medical interventions, there is a growing body of clinical evidence for a substantial, robust reduction in HF hospitalizations in various populations (clinical trial setting, post-marketing studies and real-world experiences). This review summarizes the clinical evidence, outlines future perspectives, and aims for remote patient care in heart failure using CardioMEMS. Keywords: CardioMEMS; telemonitoring; e-health; remote care; heart failure; sensor Citation: Brugts, J.J.; Radhoe, S.P.; Aydin, D.; Theuns, D.A.; Veenis, J.F. Clinical Update of the Latest Evidence for CardioMEMS Pulmonary Artery Pressure 1. Introduction Monitoring in Patients with Chronic In the last ten years, the field of heart failure has changed quite drastically. Several Heart Failure: A Promising System drugs have been proven more effective in improving prognosis of heart failure (HF) pa- for Remote Heart Failure Care. tients [1]. Device therapy and biventricular pacing is part of standard heart failure care and Sensors 2021, 21, 2335. https://doi. expanding. Still, the prevalence and incidence of heart failure are rising worldwide. This is org/10.3390/s21072335 related to the aging of the population, increasing risk factors for cardiovascular disease like obesity and the success of primary percutaneous coronary intervention (PCI) by which Received: 2 February 2021 patients survive their myocardial infarction. For Western-World countries, the chronic HF Accepted: 22 March 2021 population compromises about 1–2% of the general population [1]. In all countries, the Published: 27 March 2021 burden on hospitals for heart failure care is enormous as HF admissions, patient contacts and re-admissions are very frequent. In order to cope with these developments, remote Publisher’s Note: MDPI stays neutral care in HF is essential. The current COVID-19 pandemic might even have improved the with regard to jurisdictional claims in understanding in many healthcare systems that remote care is the way forward, with published maps and institutional affil- the aim and focus to deliver care outside the hospital to relieve the scarce resources at iations. hand. Telemonitoring and eHealth solutions are an important step to achieve these goals of remote patient care in HF. Many attempts with simple non-invasive tools of telemonitoring have been studied but proven of only small benefit with inconsistencies in literature. Still, non-invasive tools such as remote monitoring of weight or electrocardiogram (ECG) or Copyright: © 2021 by the authors. symptoms by telephone is of low cost and available to large groups of (less symptomatic) Licensee MDPI, Basel, Switzerland. patients with chronic HF [2]. Therefore, non-invasive telemonitoring tools are important to This article is an open access article study and can have a major impact on large groups. distributed under the terms and Invasive remote monitoring tools are available in HF care and consist of specially conditions of the Creative Commons developed sensors. One of the holy grails for HF therapy would be to measure filling Attribution (CC BY) license (https:// pressures remotely in a patient with heart failure. The majority of HF drugs, such as creativecommons.org/licenses/by/ 4.0/). diuretics and vasodilators, aim to lower filling pressures. It has been shown that rising

Sensors 2021, 21, 2335. https://doi.org/10.3390/s21072335 https://www.mdpi.com/journal/sensors Sensors 2021, 21, x FOR PEER REVIEW 2 of 14

Sensors 2021, 21, 2335 pressures remotely in a patient with heart failure. The majority of HF drugs, such as diu-2 of 15 retics and vasodilators, aim to lower filling pressures. It has been shown that rising filling pressures are the first hemodynamic sign of an upcoming period of decompensation. The rise in filling pressure comes well before the signs of overt clinical congestion [3]. This couldfilling provide pressures an approach are the first for hemodynamic early proactiv signe interventions of an upcoming based period uponof filling decompensation. pressures The rise in filling pressure comes well before the signs of overt clinical congestion [3]. This in a patient outside the hospital with the central aim to prevent hospitalization. The Car- could provide an approach for early proactive interventions based upon filling pressures dioMEMS HF system uses a specially developed sensor placed in the left lower lobe pul- in a patient outside the hospital with the central aim to prevent hospitalization. The monary artery (PA), and is able to measure PA pressures remotely as a surrogate for vol- CardioMEMS HF system uses a specially developed sensor placed in the left lower lobe ume status [4,5]. pulmonary artery (PA), and is able to measure PA pressures remotely as a surrogate for This review will provide an overview of the clinical evidence for the CardioMEMS volume status [4,5]. HF monitoring system in patients with chronic heart failure. This review will provide an overview of the clinical evidence for the CardioMEMS HF monitoring system in patients with chronic heart failure. 2. The CardioMEMS HF System 2. TheThe CardioMEMSCardioMEMS HF Systemsystem consists of an implantable wireless sensor, a patient and hospitalThe CardioMEMS electronics system HF system and a consists patient ofdatabase an implantable (Integrated wireless Merlin.net sensor, secure a patient web- and sitehospital for patient electronics data management). system and aThe patient sensor database measures (Integrated PA pressures Merlin.net using microelectro- secure website mechanicalfor patient system data management). technology with The a sensorpiezoele measuresctrical membrane PA pressures (wireless) using microelectrome-(Figure 1) [1– 5].chanical Distortion system of the technology piezoelectrical with amembrane piezoelectrical in the membrane sensor (in (wireless)the vessel) (Figure changes1)[ the1–5 ]. resonanceDistortion frequency of the piezoelectrical signal which corresponds membrane in to the a pressure sensor (in shift. the The vessel) sensor changes is implanted the reso- in nancea branch frequency of the signalleft pulmonary which corresponds artery through to a pressure the femoral shift. Thevein. sensor CardioMEMS is implanted is the in a onlybranch invasive of the heart left pulmonaryfailure (HF) arteryremote through monitoring the femoral sensor with vein. Food CardioMEMS and Drug isAdmin- the only istrationinvasive (FDA) heart approval failure (HF) and remote European monitoring Conformity sensor (CE) with mark. Food The and CardioMEMS Drug Administration HF system(FDA) is recommended approval and in Europeanthe European Conformity Society of (CE) Cardiology mark. The (ESC) CardioMEMS guidelines of HF 2016 system with is a classrecommended II b level B in recommendation, the European Society which of Cardiologyis expected (ESC)to be upgraded guidelines in of the 2016 newest with aver- class sionII bof level the guidelines B recommendation, in 2021 with which evid isence expected from several to be upgraded new studies in the[1,6–10]. newest version of the guidelines in 2021 with evidence from several new studies [1,6–10].

Figure 1. The CardioMEMS pulmonary artery pressure sensor and patient electronics unit for daily pressure measurements. FigureFigures 1. The used CardioMEMS with permission pulmonary from Abbott artery (Abbott, pressure Sylmar, sensor CA, and USA). patient electronics unit for daily pressure measurements. Figures used with permission from Abbott (Abbott, Sylmar, CA, USA). The CardioMEMS PA sensor has no internal power supply and is fully compatible withThe implantable CardioMEMS cardioverter PA sensor deﬁbrillators has no internal (ICDs), power (cardiac supply resynchronization and is fully compatible therapy) withCRT implantable devices and cardioverter left ventricular defibrillators assist devices (ICDs), (LVADs). (cardiac Furthermore, resynchronization the sensor therapy) is MRI CRT(magnetic devices resonanceand left ventricular imaging) compatible.assist device Potentials (LVADs). complications Furthermore, are the mostly sensor related is MRI to (magneticthe implant resonance procedure, imaging) which compatible. is of very lowPotential risk as complications will be discussed are mostly extensively related in to this thereview. implant Patients procedure, who arewhich already is of onvery anticoagulants low risk as will are restartedbe discussed on treatment extensively after in sensorthis review.implantation. Patients who Patients are already who are on not anticoagulants yet receiving are anticoagulants restarted on treatment should start after treatment sensor implantation.with aspirin Patients (81 mg/day who or are 325 not mg/day) yet receiv anding clopidogrel anticoagulants (75 mg/day) should concomitantly start treatment for 1 withmonth aspirin after (81 implant, mg/day after or 325 which mg/day) aspirin and monotherapy clopidogrel is(75 to mg/day) be continued concomitantly lifelong [ 4for]. The 1 monthneed after for anticoagulants implant, after canwhich potentially aspirin monotherapy cause adverse is (bleeding)to be continued events. lifelong The sensor [4]. The was needdeveloped for anticoagulants to last lifelong, can butpotentially several problemscause adverse have (bleeding) been encountered. events. The A case sensor report was has developeddescribed to dampened last lifelong, PA but pressure several waveforms problems monthshave been after encountered. successful implantation A case report [11 has]. In describedthis patient, dampened dampening PA pressure of the signal waveforms was most months likely causedafter successful by sensor implantation migration and [11]. was Inresolved this patient, by recalibration. dampening of Another the signal case was report most has likely described caused sensor by sensor migration, migration which and may occur during the implant procedure, but also later onwards during the monitoring phase. was resolved by recalibration. Another case report has described sensor migration, which In this case, no adverse outcomes occurred and the sensor was successfully recalibrated with repeated right heart catheterization and could therefore still be used to manage HF therapy [12]. Currently, there is no detailed information on pressure range limitations, but one study investigated CardioMEMS in patients suffering from pulmonary arterial Sensors 2021, 21, 2335 3 of 15

hypertension (PAH) with systolic PA pressures over 90 mmHg, and found the device to be feasible and safe, which is promising for the target HF population [13]. This article provides an overview of the latest promising information on using Car- dioMEMS for telemonitoring of heart failure in New York Heart Association (NYHA) class III patients. The increasing body of evidence for this technique suggests exciting opportunities to improve future heart failure management.

3. Current Evidence: Overview of Studies Currently, multiple studies have investigated the safety and clinical efﬁcacy of the CardioMEMS PA sensor in chronic HF patients. All studies are discussed in detail below, and an overview of the study characteristics and their results is provided.

CHAMPION Trial The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial, published in 2011, was the first clinical trial confirming that implantable hemodynamic monitoring systems can reduce the number of HF hospitalizations as a landmark study [4]. The CHAMPION trial studied 550 patients with chronic HF in NYHA functional class III with 1 previous HF admission in the past 12 months from 64 participating centers in the USA. The patients were randomized to the CardioMEMS HF system (n = 270) versus the control group (n = 280) and were studied for at least 6 months [4]. All patients received a CardioMEMS device implant, and were instructed to perform daily pressure readings. In the CardioMEMS HF system group, the treating physicians used the daily measurement of pulmonary artery pressures in addition to standard care with the aim to normalize PA pressures and proactively react upon significant rises in PA pressures. In the control group, treating physicians had no information on PA pressures. The primary efficacy endpoint was the rate of HF hospitalization at 6 months. The primary safety endpoint was the freedom of device- or system-related complications (DSRC) and freedom of sensor failures at 6 months. The mean age of these patients was 61 years and 73% were men. The majority of patients suffered from heart failure with a reduced ejection fraction (HFrEF), 78% with a left ventricular ejection fraction (LVEF) < 40%. On baseline, 90% of all patients received a beta-blocker, 78% a RAS-inhibitor and 42% a mineralocorticoid receptor antagonist (MRA) [4]. In 6 months, 120 HF-related hospitalizations occurred in the control group (rate 0.44) and 84 in the CardioMEMS group (0.32) which resulted in a significant reduction in HF hospitalizations of 28% (HR 0.72 95% CI 0.60–0.85; p < 0.0001). During the entire follow-up of 15 months, the treatment group had a 37% reduction in HF-related hospitalizations as compared to the control group (Figure2). Considering safety, the freedom of DSRC was 98.6% and freedom of sensor failures 100%. Clearly, the CHAMPION trial established that additional hemodynamic information is superior to clinical signs and symptoms only and allows for improved HF management remotely [4]. SensorsSensors 20212021, 21,, 21x ,FOR 2335 PEER REVIEW 4 of4 15of 14

FigureFigure 2. Short-term 2. Short-term results results from from the the CHAMPION CHAMPION trial: Cumulative heart-failure-relatedheart-failure-related hospitalizations hospitalizations during during entire entire periodperiod of randomized of randomized single-blind single-blind follow-up follow-up (A (A),), and and freedom freedom from firstfirst heart-failure-relatedheart-failure-related hospitalization hospitalization or or mortality mortality duringduring the the entire entire period period of ofrandomized randomized follow-up follow-up (B (B).). Reprinted Reprinted from The LancetLancet VolumeVolume 377, 377, Issue Issue 9766, 9766, Abraham Abraham et al.,et al., WirelessWireless pulmonary pulmonary artery artery hemodynamic hemodynamic monitoringmonitoring in in chronic chronic heart heart failure: failure: a randomized a randomized controlled controlled trial, pagestrial, pages 658–666, 658– 666, Copyright 2011, with permission from Elsevier [4]. Copyright 2011, with permission from Elsevier [4]. 4.4. Open-Access Open-Access Extension Extension of of the the CHAMPION TrialTrial AfterAfter the the randomized randomized access access period, anan open-accessopen-access period period in in the the CHAMPION CHAMPION trial trial waswas extended extended where where former former control control group patientspatients werewere also also managed managed by by using using PA PA pres- pres- suresure feedback feedback [5]. [5]. After After pulmonary pulmonary artery pressurepressure information information became became available available to to guide guide therapytherapy during during open open access access (mea (meann 13 months),months), ratesrates of of admissions admissions to to hospital hospital for for heart heart failurefailure in in the the former former control control group group were were reduced reduced by by 48% 48% (HR (HR 0·52 0.52 [95% [95% CI CI 0·40–0·69]; 0.40–0.69]; p < p < 0.0001) compared to admission rates during randomized access which confirms the 0·0001) compared to admission rates during randomized access which confirms the demonstrated benefit of the CardioMEMS HF system monitoring (Figures3 and4). Fur- demonstrated benefit of the CardioMEMS HF system monitoring (Figures 3 and 4). Fur- thermore, over the complete randomized follow-up period averaging 18 months, heart thermore,failure admission over the rates complete were significantly randomized lower follow-up in the treatment period averaging group as compared18 months, to theheart failurecontrol admission group (HR rates 0.67 [95%were CIsignificantly 0.55–0.80]; plo

SensorsSensors 20212021, 21, 21, ,x 2335 FOR PEER REVIEW 5 of 15 5 of 14

FigureFigure 3. 3.Long-term Long-term results results from from the the CHAMPION CHAMPION trial: trial: Effect Effect of continued of continued access access to pulmonary to pulmonary arteryartery pressure pressure information information on theon the change change in rates in rates of admission of admission to hospital to hospital for heart for failure heart during failure during openopen access access in in the the former former treatment treatment group group (A) and(A) onand the on change the change in rates in of rate admissions of admission to hospital to hospital forfor heart heart failure failure during during open open access access and inand the in former the former control control group ( Bgroup). Reprinted (B). Reprinted from The Lancet,from The Lan- Volumecet, Volume 387, Issue 387, 10017,Issue Abraham10017, Abraham et al., Sustained et al., Sustai efﬁcacyned of efficacy pulmonary of pulmonary artery pressure artery to guide pressure to adjustmentguide adjustment of chronic of chronic heart failure heart therapy: failure therapy: complete complete follow-up follow-up results from results the CHAMPION from the CHAM- randomizedPION randomized trial, pages trial, 453–461, pages Copyright 453–461, 2016,Copyright with permission 2016, with from permission Elsevier [from5]. Elsevier [5].

Sensors 2021 21 Sensors 2021, ,21, ,x 2335 FOR PEER REVIEW 6 of 15 6 of 14

FigureFigure 4. 4.Long-term Long-term results results from from the CHAMPION the CHAMPION trial: Effect trial: of Effect pulmonary of pulmonary artery pressure-guided artery pressure- heartguided failure heart management failure management on rates of admission on rates toof hospitaladmission (A) to and hospital on combined (A) and rates on of combined admission rates of toadmission hospital and to mortalityhospital and (B). Reprintedmortality from(B). Reprinted The Lancet, from Volume The 387, Lanc Issueet, Volume 10017, Abraham 387, Issue et al., 10017, SustainedAbraham efﬁcacy et al., ofSustained pulmonary efficacy artery pressureof pulmonary to guide artery adjustment pressure of chronic to guide heart adjustment failure therapy: of chronic completeheart failure follow-up therapy: results complete from the follow-up CHAMPION result randomizeds from the trial, CHAMPION pages 453–461, randomized Copyright 2016,trial, pages with453–461, permission Copyright from Elsevier2016, with [5]. permission from Elsevier [5].

4.1. MEMS-HF PA pressure-guided HF management using the CardioMEMS HF system had been shown to be safe, reliable and effective in reducing HF hospitalizations in patients with chronic heart failure in NYHA class III only in the U.S. healthcare system. Considering the substantial differences in healthcare system organization, the question rose whether the

Sensors 2021, 21, 2335 7 of 15

4.1. MEMS-HF PA pressure-guided HF management using the CardioMEMS HF system had been Sensors 2021, 21, x FOR PEER REVIEW 7 of 14 shown to be safe, reliable and effective in reducing HF hospitalizations in patients with chronic heart failure in NYHA class III only in the U.S. healthcare system. Considering the substantial differences in healthcare system organization, the question rose whether findingsthe ﬁndings could could be extrapolated be extrapolated to Europe to Europe and be and replicated be replicated outside outside the U.S. the The U.S. Cardi- The oMEMSCardioMEMS European European Monitoring Monitoring Study for Study Heart for Failure Heart (MEMS-HF) Failure (MEMS-HF) study was study a prospec- was a prospective,tive, non-randomized, non-randomized, multicenter multicenter study perf studyormed performed in sites from in sites Germany, from Germany, the Nether- the landsNetherlands and Ireland and and Ireland was and published was published in 2020 [6]. in The 2020 MEMS-HF [6]. The MEMS-HF study studied study 234 studied NYHA class234 NYHA III patients class with III patients ≥1 HF admission with ≥1 HF in admissionthe past 12 in months. the past The 12 primary months. outcome The primary was theoutcome reduction was thein HF reduction hospitalizations. in HF hospitalizations. The primary Thesafety primary endpoint safety was endpoint the freedom was the of DSRCfreedom and of freedom DSRC and of freedomsensor failures of sensor at 1 failures year. In at addition, 1 year. In quality addition, of life quality was ofstudied life was in morestudied detail in more using detail the Kansas using the City Kansas Cardio Citymyopathy Cardiomyopathy Questionnaire Questionnaire (KCCQ). (KCCQ). The MEMS- The HFMEMS-HF was a post-marketing was a post-marketing surveillance surveillance prospective prospective study without study randomization, without randomization, in which patientsin which were patients their were own their historical own historical controls (using controls the (using event the rate event of the rate year of thepre-implant year pre- versusimplant the versus year post the year implant post of implant Cardio-MEMS). of Cardio-MEMS). At 12 months’ At 12 follow-up, months’ follow-up,the rate of theHF hospitalizationrate of HF hospitalization was reduced was by reduced62% with by pu 62%lmonary with artery pulmonary pressure artery (PAP) pressure monitoring. (PAP) Themonitoring. freedom The of freedomDSRC at of1 DSRCyear was at 1 98.3% year was and 98.3% freedom and freedomof sensor of failures sensor failureswas 99.6%, was which99.6%, confirms which conﬁrms the safety the and safety durability and durability of this oftechnology this technology (Figure (Figure 5). Considering5). Considering qual- qualityity of life, of life,the KCCQ the KCCQ overall overall summary summary score score improved improved from from 47 at 47 baseline at baseline to 60.5 to 60.5(p < (0.001),p < 0.001), which which is considerable is considerable and andclinically clinically meaningful meaningful improvement improvement (Figure (Figure 6) [6].6)[ 6].

Figure 5.5. AnnualizedAnnualized heart-failure-relatedheart-failure-related hospitalization hospitalization rates rates pre-implant pre-implant and and post-implant post-implant as as reported reported in thein the MEMS-HF MEMS- study.HF study. Reprinted Reprinted from from the the European European Journal Journal of of Heart Heart Failure, Failure, Volume Volume 22, 22, Issue Issue 10, 10, Angermann Angermann et et al., al., PulmonaryPulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF), pages 1891–1901, with permission from Wiley [6]. Study for Heart Failure (MEMS-HF), pages 1891–1901, with permission from Wiley [6].

SensorsSensors 20212021, 21,,21 x ,FOR 2335 PEER REVIEW 8 of8 15of 14

FigureFigure 6. Changes 6. Changes in patient-reported in patient-reported outcomes outcomes by bybaseline baseline mean mean pulmonary pulmonary artery artery pressure pressure (m (mPAP)PAP) as as reported reported in in the MEMS-HFthe MEMS-HF study. study.CSS, clinical CSS, clinical summary summary score; score; KCCQ, KCCQ, Kansas Kansas City CityCardiomyopathy Cardiomyopathy Questi Questionnaire;onnaire; OSS, OSS, overall overall sum- marysummary score; PHQ-9, score; PHQ-9, 9-item 9-itemPatient Patient Health Health Questionnaire; Questionnaire; VAS, visual VAS, visual analogue analogue scale. scale.Reprinted Reprinted from the from European the European Journal of HeartJournal Failure, of Heart Volume Failure, 22, Volume Issue 10, 22, Ange Issuermann 10, Angermann et al., Pulmonary et al., Pulmonary artery pressure artery pressure-guided-guided therapy therapy in ambulatory in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF), pages 1891– patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF), pages 1901, with permission from Wiley [6]. 1891–1901, with permission from Wiley [6].

4.2.4.2. The The CardioMEMS CardioMEMS Post-Approval Post-Approval Study (PAS)(PAS) TheThe PAS PAS was was a a multicenter multicenter prospective open-labelopen-label study study performed performed in in 1200 1200 chronic chronic HFHF patients patients with with a a prior prior HF HF admission withinwithin 1212 months months from from 104 104 sites sites from from the the United United StatesStates and and published published its its main main results inin 2020.2020. PatientsPatients were were selected selected irrespective irrespective of of their their HFHF subtype subtype and and ejection ejection fraction percentage.percentage. Again,Again, the the hospitalization hospitalization rates rates during during the the firstfirst 12 12 months months postpost CardioMEMS CardioMEMS implantation implantation were were compared compared to the to hospitalization the hospitalization rates ratesduring during the 12the months 12 months prior prior to CardioMEMS to CardioMEMS implantation. implantation. These These patients patients had a meanhad a agemean of 69 years and 62% were men. Background HF therapy (beta-blockers, RAS inhibitors, age of 69 years and 62% were men. Background HF therapy (beta-blockers, RAS inhibi- mineralocorticoid receptor antagonists (MRA) and ICD therapy) in HFrEF patients was tors, mineralocorticoid receptor antagonists (MRA) and ICD therapy) in HFrEF patients contemporary and adequate [7]. The rate of HF hospitalization was significantly reduced waswith contemporary PA monitoring and by adequate the CardioMEMS [7]. The HFrate system of HF byhospitalization 57% (HR 0.43; was 95% significantly CI 0.39–0.47, re- ducedp < 0.0001) with PA [7]. monitoring The freedom by the of device-CardioMEMS or system-related HF system complicationsby 57% (HR 0.43; at 1 95% year CI was 0.39– 0.47,99.6% p < and0.0001) freedom [7]. The from freedom sensor of failure device- at 1or year system-related was 99.9% (Figurecomplications7)[ 7]. Theat 1 rateyear of was 99.6%all-cause and hospitalizationfreedom from wassensor significantly failure at lower1 year at was 1 year 99.9% compared (Figure with 7) [7]. the The year rate before of all- causeimplantation hospitalization as well. was A striking significantly result that lower was at shown 1 year in compared this analysis with is thatthe year the benefit before of im- plantationthe CardioMEMS as well. HFA striking system is result independent that was of shown ejection in fraction this analysis and a significant is that the reduction benefit of thewas CardioMEMS shown in patients HF system with heart is independent failure witheither of ejection reduced fraction or preserved and a ejectionsignificant fraction reduc- tionacross was all shown EF% ranges in patients (EF < 40%;with EFheart 40–50% failur ande with EF > either 50%) [ 7reduced]. No previous or preserved treatments ejection or fractionmonitoring across strategies all EF% haveranges shown (EF < any 40%; benefit EF 40–50% in patients andwith EF>50%) preserved [7]. No EF. previous Monitoring treat- mentsPA pressures or monitoring as surrogate strategies of filling have pressures shown andany volume benefit status in patients is intuitive with and preserved clinically EF. Monitoring PA pressures as surrogate of filling pressures and volume status is intuitive and clinically plausible to be effective in preventing overt clinical congestion in heart failure patients with preserved ejection fraction (HFpEF) [7].

Sensors 2021, 21, 2335 9 of 15

Sensors 2021, 21, x FOR PEER REVIEW 9 of 14 plausible to be effective in preventing overt clinical congestion in heart failure patients with preserved ejection fraction (HFpEF) [7].

FigureFigure 7. Heart 7. Heart failure failure hospitalization hospitalization (HFH) (HFH) rates rates before before and and afte afterr pulmonary arteryarterypressure pressure sensor sensor implantation implantation as as reportedreported in the in the CardioME CardioMEMSMS Post-Approval-Study. Post-Approval-Study. ((AA)) 6 6 month month cohort, cohort, (B ()B 12) 12 month month cohort. cohort. Reprinted Reprinted from from the Journalthe Journal of of thethe American American College College of Cardiology, VolumeVolume 69, 69, Issue Issue 19, 19, Desai Desai et et al., al., Ambulatory Ambulatory Hemodynamic Hemodynamic Monitoring Monitoring Reduces Reduces HeartHeart Failure Failure Hospitalizations Hospitalizations in in“Rea “Real-World”l-World” Clinical Clinical Practice, Practice, pages 2357–2365,2357–2365,Copyright Copyright 2017, 2017, with with permission permission from from ElsevierElsevier [9]. [ 9].

4.3. The COAST Study 4.3. The COAST Study In Europe, another post-marketing surveillance study is currently ongoing and some In Europe, another post-marketing surveillance study is currently ongoing and some of the first-year results have been published in 2020. The CardioMEMS Post-Market Study of the first-year results have been published in 2020. The CardioMEMS Post-Market Study (COAST)(COAST) study study aims aims to to investigate investigate the the effectiv effectivenesseness ofof thethe CardioMEMS CardioMEMS system system in in a post-a post- marketingmarketing setting setting in in Europe Europe [8 [8].]. It It includes includes NYHANYHA classclass IIIIII chronic chronic HF HF patients patients with with HFrEF,HFrEF, heart heart failure failure with with midrange midrange ejection fractionfraction (HFmrEF)(HFmrEF) or or HFpEF, HFpEF, with with at at least least 1 1 HF-relatedHF-related hospitalization hospitalization in in the the last last year. In 2020,2020, thetheresults results from from the the first first 100 100 patients patients fromfrom the the United United Kingdom Kingdom (UK) (UK) included included in in the the COAST COAST study study have have been been presented presented in in an abstractan abstract at the at 2020 the 2020 ESC ESC Heart Heart Failure Failure congress congress [8]. [8 These]. These patients patients had had a amean mean age age of of 69 years,69 years, and 70% and were 70% weremen. men.In these In thesefirst 100 first patients, 100 patients, 1% of 1% all ofpatients all patients developed developed a sensor- a orsensor- procedure-related or procedure-related complication, complication, and 1% andhad 1%a sensor had a failure sensor failureduring during the first the 6 firstmonths 6 ofmonths follow-up. of follow-up. A large reduction A large reduction in the HF-related in the HF-related hospitalization hospitalization rate ratewas wasobserved observed (2.05 HF-related(2.05 HF-related hospitalizations/patient-year hospitalizations/patient-year during during the 6 the months 6 months prior prior to toCardioMEMS CardioMEMS im- plantationimplantation vs. 0.33 vs. 0.33HF-related HF-related hospitalizations/patient-year hospitalizations/patient-year during during the the 6 months 6 months post post Car- CardioMEMS implantation) [8]. This initial interim analysis confirms the previously shown dioMEMS implantation) [8]. This initial interim analysis confirms the previously shown benefit of the CardioMEMS HF system in reducing HF hospitalization in Europe. benefit of the CardioMEMS HF system in reducing HF hospitalization in Europe. 4.4. Real-World Studies 4.4. Real-World Studies Several studies have examined the effectiveness of ambulatory hemodynamic moni- toringSeveral by the studies CardioMEMS have examined HF system the in effectiveness reducing HF hospitalizationof ambulatory outsidehemodynamic strict clinical moni- toringtrials by or the prospective CardioMEMS study HF settings system [9, 10in]. reducing Desai et HF al. conductedhospitalization a retrospective outside strict cohort clinical trials or prospective study settings [9,10]. Desai et al. conducted a retrospective cohort study using 1114 patients from the U.S. Medicare claims database who had a Cardi- oMEMS sensor implanted between 1 June 2014 and 31 December 2015 [9]. The investigators identified 1020 HF-related hospitalizations in the 1114 patients in the 6 months prior to receiving a CardioMEMS sensor implant and 381 HF hospitalizations, 139 deaths and 17 left ventricular assist devices or heart transplants (competing risks) in the 6 months

Sensors 2021, 21, 2335 10 of 15

study using 1114 patients from the U.S. Medicare claims database who had a CardioMEMS sensor implanted between 1 June 2014 and 31 December 2015 [9]. The investigators identi- ﬁed 1020 HF-related hospitalizations in the 1114 patients in the 6 months prior to receiving Sensors 2021, 21, x FOR PEER REVIEW 10 of 14 Sensors 2021, 21, x FOR PEER REVIEWa CardioMEMS sensor implant and 381 HF hospitalizations, 139 deaths and 17 left10 of ven- 14

tricular assist devices or heart transplants (competing risks) in the 6 months after implant, which resulted in a 45% reduction in cumulative heart failure hospitalizations observed 6 after implant, which resulted in a 45% reduction in cumulative heart failure hospitaliza- aftermonths implant, after PAPwhich sensor resulted implant in a 45% versus reduction in the 6 in months cumulative prior toheart implantation failure hospitaliza- (HR 0.55, tions observed 6 monthsp after PAP sensor implant versus in the 6 months prior to implan- tions95% observed CI 0.49–0.61; 6 months< 0.001) after PAP [9]. Insensor those impl patientsant versus with in complete the 6 months follow-up prior to data implan- at 12 tationmonths (HR (n =0.55, 480), 95% results CI 0.49–0.61; were similar p < 0.001) with [9]. a 34% In those risk reduction patients with (Figure complete7) (HR follow-up 0.66, 95% tation (HR 0.55, 95% CI 0.49–0.61; p < 0.001) [9]. In those patients with complete follow-up dataCI 0.57–0.76). at 12 months This (n Medicare = 480), results analysis were confirms similar the with treatment a 34% risk benefit reduction of the (Figure CardioMEMS 7) (HR data at 12 months (n = 480), results were similar with a 34% risk reduction (Figure 7) (HR 0.66,HF system 95% CI monitoring 0.57–0.76). outsideThis Medicare the clinical analys trialis settingconfirms [9 ].the treatment benefit of the Car- 0.66, 95% CI 0.57–0.76). This Medicare analysis confirms the treatment benefit of the Car- dioMEMSA second HF system matched-cohort monitoring study outside from the the clinical Medicare trial setting beneficiaries’ [9]. claims database dioMEMS HF system monitoring outside the clinical trial setting [9]. betweenA second 1 June matched-cohort 2014 and 31 March study 2016 from studied the Medi 1087care patients beneficiaries’ who received claims an database implantable be- A second matched-cohort study from the Medicare beneficiaries’ claims database be- tweenPA sensor 1 June and 2014 1087 and matched 31 March control 2016 patientsstudied 1087 [10]. patients Comparing who thereceived rates ofan HFimplantable hospital- tween 1 June 2014 and 31 March 2016 studied 1087 patients who received an implantable PAization sensor during and 1087 the 12matched months control after CardioMEMSpatients [10]. Comparing implantation the between rates of HF treatment hospitaliza- and PA sensor and 1087 matched control patients [10]. Comparing the rates of HF hospitaliza- tioncontrol during group, the the12 months authors after demonstrated CardioMEMS a reduction implantation of 24% between (HR 0.76 treatment 95% CI and 0.65–0.89). control tion during the 12 months after CardioMEMS implantation between treatment and control Thesegroup, Medicare the authors analyses demonstrated confirm thea reductio efficacyn ofof the24% CardioMEMS (HR 0.76 95% HF CI system 0.65–0.89). in the These real group, the authors demonstrated a reduction of 24% (HR 0.76 95% CI 0.65–0.89). These worldMedicare outside analyses of clinical confirm trial the settings. efficacy Several of the smallerCardioMEMS studies HF of singlesystem centers in the real-worldreal world Medicare analyses confirm the efficacy of the CardioMEMS HF system in the real world outsideexperiences of clinical have reportedtrial settings. similar Several effects smaller and safety studies [14 ].of single centers real-world expe- outside of clinical trial settings. Several smaller studies of single centers real-world expe- riencesFigures have 8reported and9 provide similar aeffects summary and safety overview [14]. of the safety and durability of the riences have reported similar effects and safety [14]. CardioMEMSFigures 8 and HF system9 provide from a summary all reported overview studies of providingthe safety and data durability on these of issues. the Car- In Figures 8 and 9 provide a summary overview of the safety and durability of the Car- dioMEMSgeneral, the HF implant system procedure from all re isported very safe studies with providing >98% freedom data fromon these DSRC, issues. and In the general, sensor dioMEMS HF system from all reported studies providing data on these issues. In general, theis durable implant with procedure a very lowis very number safe with of sensor >98% failuresfreedom at from 1 year DSRC, (>99% and freedom the sensor of sensor is du- the implant procedure is very safe with >98% freedom from DSRC, and the sensor is du- rablefailures). with a very low number of sensor failures at 1 year (>99% freedom of sensor failures). rable with a very low number of sensor failures at 1 year (>99% freedom of sensor failures).

Figure 8.8. OverviewOverview ofof thethe safetysafety (freedom (freedom of of device- device- or or system-related system-related complications complications at 12at months)12 months) of theof the CardioMEMS CardioMEMS HF Figure 8. Overview of the safety (freedom of device- or system-related complications at 12 months) of the CardioMEMS HF system as reported in clinical studies. HFsystem system as reportedas reported in clinical in clinical studies. studies.

Figure 9. Overview of the reliability (freedom of sensor failures at 12 months) of the CardioMEMS HF system as reported FigureFigure 9. 9. OverviewOverview of of the reliability (freedom ofof sensorsensor failuresfailures atat 12 12 months) months) of of the the CardioMEMS CardioMEMS HF HF system system as as reported reported in in clinical studies. inclinical clinical studies. studies. Figure 10 provides an overview of the clinical efficacy in reducing HF hospitaliza- FigureFigure 10 provides anan overviewoverview of of the the clinical clinical efﬁcacy efficacy in in reducing reducing HF HF hospitalizations hospitalizations by the CardioMEMS HF monitoring system in all reported studies. In general, the tionsby the by CardioMEMS the CardioMEMS HF monitoring HF monitoring system system in all reported in all reported studies. Instudies. general, In thegeneral, treatment the treatment benefit of PA monitoring is evident and consistent from trial data to post-mar- treatment benefit of PA monitoring is evident and consistent from trial data to post-marketing surveillance data to real-world data. In addition, the benefit of CardioMEMS is keting surveillance data to real-world data. In addition, the benefit of CardioMEMS is shown across various types of HF patients and across EF% ranges. shown across various types of HF patients and across EF% ranges.

Sensors 2021, 21, 2335 11 of 15

beneﬁt of PA monitoring is evident and consistent from trial data to post-marketing Sensors 2021, 21, x FOR PEER REVIEWsurveillance data to real-world data. In addition, the beneﬁt of CardioMEMS is shown11 of 14

across various types of HF patients and across EF% ranges.

FigureFigure 10.10.Overview Overview ofof thethe clinicalclinical efﬁcacyefficacy inin reducingreducing HFHF hospitalizationshospitalizations byby thethe CardioMEMSCardioMEMS HFHF systemsystem asas reportedreported in in clinicalclinical studies. studies. Legend: Legend: red red and and orange orange bars bars indicate indicate either either control control group group or theor the historical historical controls; controls; green green bars bars indicate indicate the the active CardioMEMS patient group; * Indicates event rate per patient per 6 months. active CardioMEMS patient group; * Indicates event rate per patient per 6 months.

AnAn overviewoverview ofof thethe studystudy characteristicscharacteristics andand theirtheir resultsresults isis shownshown inin TableTable1 .1.

Table 1. Overview of study characteristics and patient baseline variables of CardioMEMS studies.

Study Characteristics Patient Baseline Variables * Year of Follow- Number Background HF Therapy (%) First Countr Publicati up of Mean Age Male (%) Beta- Author y RAS-i MRA on Duration Patients Blockers Randomized

controlled trials CHAMPION

trial CM: Open- CM: 72 CM: 89 CM: 76 CM: 43 Abraham 13 61.3±13.0 access/extended 2016 USA 347** Control: Control: Control: Control: 4 months Control: period 73 84 79 41 61.8±12.7 CM: CM: 72 CM: 90 CM: 76 CM: 43 Randomized Abraham 61.3±13.0 2011 USA 6 months 550 Control: Control: Control: Control: access period 5 Control: 73 91 79 41 61.8±12.7 Non- randomized

controlled studies Angerma DE/NL/ 12 MEMS-HF 2020 234 67.9±10.7 78.2 88.9 85.5 72.2 nn6 IE months 12 PAS Shavelle7 2020 USA 1200 69±12.0 62.3 88.1 56.9 44.1 months COAST Cowie8 2020 UK 6 months 100 69±12 70 NA NA NA

Desai9 2017 USA 6 months 1114 71.3±10.8 63.8 NA NA NA 12 Real-world 480 71.4±11.4 62.5 NA NA NA months studies CM: 35.1 Abraham 12 CM: 2019 USA 2174 Control: NA NA NA 10 months 62.7±10.2 35.1

Sensors 2021, 21, 2335 12 of 15

Table 1. Overview of study characteristics and patient baseline variables of CardioMEMS studies.

Study Characteristics Patient Baseline Variables *

Year of Follow-Up Number of Background HF Therapy (%) First Author Country Mean Age Male (%) Publication Duration Patients Beta-Blockers RAS-i MRA Randomized controlled trials CHAMPION trial Open- access/ CM: 61.3 ± 13.0 CM: 72 CM: 89 CM: 76 CM: 43 Abraham 4 2016 USA 13 months 347 ** extended period Control: 61.8 ± 12.7 Control: 73 Control: 84 Control: 79 Control: 41 Randomized access CM: 61.3 ± 13.0 CM: 72 CM: 90 CM: 76 CM: 43 Abraham 5 2011 USA 6 months 550 period Control: 61.8 ± 12.7 Control: 73 Control: 91 Control: 79 Control: 41 Non-randomized controlled studies MEMS-HF Angermann 6 2020 DE/NL/IE 12 months 234 67.9 ± 10.7 78.2 88.9 85.5 72.2 PAS Shavelle 7 2020 USA 12 months 1200 69 ± 12.0 62.3 88.1 56.9 44.1 COAST Cowie 8 2020 UK 6 months 100 69 ± 12 70 NA NA NA

Desai 9 2017 USA 6 months 1114 71.3 ± 10.8 63.8 NA NA NA Real-world studies 12 months 480 71.4 ± 11.4 62.5 NA NA NA CM: 62.7 ± 10.2 CM: 35.1 Abraham 10 2019 USA 12 months 2174 NA NA NA Control: 72.9 ± 10.1 Control: 35.1 Assaad 14 2019 USA 6–18 months 27 67 ± 12 52 92.6 77.8 33.3 CHAMPION, CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients; COAST, CardioMEMS Post-Market Study; DE, Germany; IE, Ireland; NL, Netherlands; HF, heart failure; CM, CardioMEMS; MEMS-HF, CardioMEMS European Monitoring Study for Heart Failure; MRA, mineralocorticoid receptor antagonist; NA, not available; PAS, Post Approval Study; RAS-i, renin-angiotensin system inhibitors; UK, United Kingdom; USA, United States of America.* All studies were performed in patients suffering from chronic heart failure in NYHA class III across all ejection fraction ranges with a previous HF-related hospitalization. ** Primary efﬁcacy analysis was performed in a subset of 347 from the 550 initially enrolled patients. Sensors 2021, 21, 2335 13 of 15

5. Ongoing CardioMEMS Projects 5.1. The GUIDE HF Trial In the United States, the GUIDE HF trial is currently enrolling and intends to test the efficacy of the CardioMEMS HF system in an expanded population, including patients outside the current indication of NYHA III but at risk of future HF events (ClinicalTrials.gov Identifier: NCT03387813) [15]. The trial will include 3600 patients with NYHA functional class II, III and IV and uses the criteria of either a prior HF hospitalization or a currently elevated NT-proBNP level above certain thresholds. Results are expected in 2021. The subgroup of NYHA class II HF patients is particularly interesting, as it has potential to significantly broaden the indications for CardioMEMS implantation.

5.2. The MONITOR HF Trial In the Netherlands, the MONITOR HF (Hemodynamic Monitoring In Heart Failure) trial started enrollment on 1 April 2019 and is currently enrolling patients in NYHA functional class III with 1 HF hospitalization within 12 months, deﬁned as an admission for HF longer than 6 h and/or use of i.v. diuretics or emergency ward visit for HF resulting in i.v. diuretic therapy, independent of EF% (Clinical Trial Registration number NTR7672.) [16]. The MONITOR HF trial is a conditional reimbursement project to show the efﬁcacy in a Western European setting against optimal contemporary heart failure therapy in a country with structured and dedicated HF care and outpatient clinics [16]. The MONITOR HF trial primarily investigates the experienced quality of life of HF patients in detail, as well as the number of HF hospitalizations and costs associated with remote monitoring.

6. Potential Use of Hybrid Constructions of Current Therapies with CardioMEMS Monitoring Intuitively, the use of a remote hemodynamic monitoring tool provides unique opportunities for further research. For example, the effects of newer drugs like sacubitril-valsartan or sodium-glucose co-transporter-2 inhibitors prescribed in the outpatient clinic can be evaluated daily based on direct hemodynamic feedback, whereas this is conventionally assessed by judging patient status, laboratory values and echocardiography parameters which do not always accurately reﬂect hemodynamic status. Valvular heart disease, such as mitral regurgitation and aortic regurgitation, may generate volume overload and an increase in PA pressures without causing actual signs of congestion in the patient. In these cases, CardioMEMS may help assess the need for valvular intervention based on hemodynamic parameters, especially when drug interventions are unsuccessful in reverting pulmonary hypertension. After valvular intervention, CardioMEMS can accurately assess the hemodynamic effects of the intervention on a daily basis, which was not possible before. Furthermore, the PA pressure measurements can help titrate HF drugs as described in an example case report [17]. Finally, an attempt has been made to test the feasibility of combining remote hemodynamic monitoring in patients on LVAD support in the HEMO- VAD pilot study [18]. This study focussed on hemodynamic optimization, especially with diuretics, based upon PA pressures before surgery (to truly decongest the right ventricle and kidney in order to improve post-operative outcomes) and tests the feasibility of using CardioMEMS in the outpatient clinic phase of LVAD patients for assessment of volume status, arrhythmias and other VAD related complications [18–20]. A larger pivotal trial is underway in the U.S. to test the clinical use of CardioMEMS in optimization of LVAD support (INTELLECT2 trial, ClinicalTrials.gov Identiﬁer: NCT03247829).

7. Future Perspectives In 2021, several updates to the European Society of Cardiology and U.S. HF guidelines are expected, with a potential change in recommendations on CardioMEMS after the MEMS-HF and PAS data as well as real-world experiences. Additional research is needed to assess which patients are most likely to beneﬁt from a PA sensor. In the upcoming years, the CardioMEMS HF system will most likely be upgraded with a CardioMEMS app, which is Sensors 2021, 21, 2335 14 of 15

already being used in the United States. With increasing numbers of CardioMEMS implan- tations, over 20,000 in the USA in 2020, efforts need to be made to improve infrastructure for large-scale programs to maximize efﬁciency. A management-by-exception approach focusing on patients who are above their pressure threshold and reducing monitoring time in those patients within normal PA pressure range would be ideal. Currently, there are no structured treatment algorithms. Constructing such algorithms is a very complex issue, because they should provide therapy suggestions on an individual basis considering differences in treatment tolerance, blood pressure, renal function and many other comorbidities. Hospitals need to assess their telemonitoring platform or infrastructure in order to derive maximum beneﬁt from ambulatory hemodynamic monitoring as well as reduce resource utilization and healthcare costs.

8. Conclusions For patients with chronic heart failure in NYHA functional class III and a previous HF admission, the CardioMEMS HF system is a safe, reliable and proven clinically effective monitoring strategy to prevent HF hospitalizations. The beneﬁt of remote monitoring using PA pressures has been shown across all EF ranges, including HFrEF and HFpEF. Monitoring of heart failure status by CardioMEMS is based on ﬁlling pressures instead of symptoms or bodyweight, and interventions mainly consist of remote optimization of diuretic or vasodilator doses. Clearly, by preventing HF hospitalizations using hemodynamic sensors such as CardioMEMS, future heart failure care can be optimized and healthcare resources better utilized for patients in need. In addition, costs of medical care can be reduced by preventing HF admissions via proactive early interventions.

Author Contributions: J.J.B.: Writing—Original Draft Preparation and Visualization; S.P.R.: Writing– Review and Editing; D.A.: Writing—Review and Editing; D.A.T.: Writing–Review and Editing; J.F.V.: Writing—Review and Editing. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Not applicable. Conﬂicts of Interest: J.J.B. reports independent research grants from Abbott and speaker fees. S.P.R., D.A., D.A.T., J.F.V. report no conﬂict of interest.

References 1. Ponikowski, P.; Voors, A.A.; Anker, S.D.; Bueno, H.; Cleland, J.G.; Coats, A.J.; Van Der Meer, P. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur. Heart J. 2016, 37, 2129–2200. [CrossRef][PubMed] 2. Veenis, J.F.; Brugts, J.J. Remote monitoring of chronic heart failure patients: Invasive versus non-invasive tools for optimising patient management. Neth. Heart J. 2020, 28, 3–13. [CrossRef][PubMed] 3. Adamson, P.B. Pathophysiology of the transition from chronic compensated and acute decompensated heart failure: New insights from continuous monitoring devices. Curr. Heart Fail. Rep. 2009, 6, 287–292. [CrossRef][PubMed] 4. Abraham, W.T.; Adamson, P.B.; Bourge, R.C.; Aaron, M.F.; Costanzo, M.R.; Stevenson, L.W.; Strickland, W.; Neelagaru, S.; Raval, N.; Krueger, S.; et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: A randomised controlled trial. Lancet 2011, 377, 658–666. [CrossRef] 5. Abraham, W.T.; Stevenson, L.W.; Bourge, R.C.; Lindenfeld, J.A.; Bauman, J.G.; Adamson, P.B. Sustained efﬁcacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: Complete follow-up results from the CHAMPION randomised trial. Lancet 2016, 387, 453–461. [CrossRef] 6. Angermann, C.E.; Assmus, B.; Anker, S.D.; Asselbergs, F.W.; Brachmann, J.; Brett, M.E.; Brugts, J.J.; Ertl, G.; Ginn, G.; Hilker, L.; et al. Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Eur. J. Heart Fail. 2020, 22, 1891–1901. [CrossRef][PubMed] 7. Shavelle, D.M.; Desai, A.S.; Abraham, W.T.; Bourge, R.C.; Raval, N.; Rathman, L.D.; Heywood, J.T.; Jermyn, R.A.; Pelzel, J.; Jonsson, O.T.; et al. Lower Rates of Heart Failure and All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Sensors 2021, 21, 2335 15 of 15

Therapy for Ambulatory Heart Failure: One-Year Outcomes from the Cardi-oMEMS Post-Approval Study. Circ. Heart Fail. 2020, 13, e006863. [CrossRef][PubMed] 8. Cowie, M. Heart Failure hospitalisation reduction with remote Pulmonary Artery Pressure monitoring 12 months results of the ﬁrst 100 United Kingdom patients in the CardioMEMS HF System Outside-US Post-Market Study (COAST). Eur. J. Heart Fail. 2020, 22 (Suppl. S1), 2–415. [CrossRef] 9. Desai, A.S.; Bhimaraj, A.; Bharmi, R.; Jermyn, R.; Bhatt, K.; Shavelle, D.; Redﬁeld, M.M.; Hull, R.; Pelzel, J.; Davis, K.; et al. Ambulatory Hemodynamic Monitoring Reduces Heart Failure Hospitalizations in "Real-World" Clinical Practice. J. Am. College Cardiol. 2017, 69, 2357–2365. [CrossRef][PubMed] 10. Abraham, J.; Bharmi, R.; Jonsson, O.; Oliveira, G.H.; Artis, A.; Valika, A.; Capodilupo, R.; Adamson, P.B.; Roberts, G.; Dalal, N.; et al. Association of Ambulatory Hemodynamic Monitoring of Heart Failure with Clinical Outcomes in a Concurrent Matched Cohort Analysis. JAMA Cardiol. 2019, 4, 556–563. [CrossRef][PubMed] 11. Singh, R.; Scarfone, S.; Zughaib, M. Wedged Sensor in Distress? Lessons Learned from Troubleshooting Dampened Transmitted PA Waveforms of CardioMEMS Device. Case Rep. Cardiol. 2020, 2020, 3856940. [CrossRef][PubMed] 12. Rali, A.S.; Shah, Z.; Sauer, A.; Gupta, K. Late Migration of a CardioMEMSTM Wireless Pulmonary Artery Hemodynamic Monitoring Sensor. Circ. Heart Fail. 2017, 10, e003948. [CrossRef][PubMed] 13. Benza, R.L.; Doyle, M.; Lasorda, D.; Parikh, K.S.; Correa-Jaque, P.; Badie, N.; Ginn, G.; Airhart, S.; Franco, V.; Kanwar, M.K.; et al. Monitoring Pulmonary Arterial Hypertension Using an Implantable Hemodynamic Sensor. Chest 2019, 156, 1176–1186. [CrossRef][PubMed] 14. Assaad, M.; Sarsam, S.; Naqvi, A.; Zughaib, M. CardioMems® device implantation reduces repeat hospitalizations in heart failure patients: A single center experience. JRSM Cardiovasc. Dis. 2019, 8, 2048004019833290. [CrossRef][PubMed] 15. Lindenfeld, J.; Abraham, W.T.; Maisel, A.; Zile, M.; Smart, F.; Costanzo, M.R.; Mehra, M.R.; Ducharme, A.; Sears, S.F.; Desai, A.S.; et al. Hemodynamic-GUIDEd management of Heart Failure (GUIDE-HF). Am. Heart J. 2019, 214, 18–27. [CrossRef][PubMed] 16. Brugts, J.J.; Veenis, J.F.; Radhoe, S.P.; Linssen, G.C.M.; van Gent, M.; Borleffs, C.J.W.; van Ramshorst, J.; van Pol, P.; Tukkie, R.; Spee, R.F.; et al. A randomised comparison of the effect of haemodynamic monitoring with CardioMEMS in addition to standard care on quality of life and hospitalisations in patients with chronic heart failure: Design and rationale of the MONITOR HF multicentre randomised clinical trial. Neth. Heart J. 2020, 28, 16–26. [PubMed] 17. Veenis, J.F.; Van Mieghem, N.M.; Caliskan, K.; Manintveld, O.C.; Brugts, J.J. Monitoring pulmonary artery pressure in chronic heart failure patients and evaluating the treatment effect of MitraClip implantation for functional mitral regurgitation. EuroIntervention 2019, 15, 418–419. [CrossRef][PubMed] 18. Veenis, J.F.; Manintveld, O.C.; Constantinescu, A.A.; Caliskan, K.; Birim, O.; Bekkers, J.A.; van Mieghem, N.M.; den Uil, C.A.; Boersma, E.; Lenzen, M.J.; et al. Design and rationale of haemodynamic guidance with CardioMEMS in patients with a left ventricular assist device: The HEMO-VAD pilot study. ESC Heart Fail. 2019, 6, 194–201. [CrossRef][PubMed] 19. Veenis, J.F.; Birim, O.; Brugts, J.J. Pulmonary artery pressure telemonitoring by CardioMEMS in a patient pre- and post-left ventricular assist device implantation. Eur. J. Cardiothorac. Surg. 2019, 56, 809–810. [CrossRef][PubMed] 20. Veenis, J.F.; Radhoe, S.; van Mieghem, N.; Zijlstra, F.; Brugts, J.J. Remote hemodynamic guidance before and after LVAD implantation: Short term results from the HEMO-VAD pilot study. Future Cardiol. 2021.[CrossRef][PubMed]