Proactive Management of Heart Failure by Digital Health: Is Monitoring of Invasive Pulmonary Artery Pressure the Holy Grail?

This article refers to ‘Digital health care solution for proactive heart failure management with the Cordella Heart Failure System: results of the SIRONA first-in-human study’ by W. Mullens et al., published in this issue on pages 1912–1919. It is widely accepted that about half of heart failure (HF) hospitalizations are a direct consequence of inadequate self-care behavior.1 Digital and more specifically mHealth, i.e. medical and public health practice supported by mobile devices, could have an important favourable effect in enhancing self-care behaviour in HF. Over the last years, remote monitoring of vital signs [telemedicine (TM)] has been largely studied in patients suffering from HF2-4 with conflicting results. TM and patient remote management, in principle, may allow health care professionals to provide a proactive guided surveillance optimizing treatment further and prevent clinical deterioration. However, numerous TM programmes which were based on remote signs of clinical congestion such as weight or symptoms or impedance measurements through pacemakers have been partially disappointing. Several critical aspects can help to understand the reasons why many studies have failed to demonstrate a clinical benefit of TM in HF care5: (i) the choice of the appropriate clinical parameters to monitor, since weight gain, shortness of breath, paroxysmal nocturnal dyspnoea, might be late manifestations of congestion and worsening HF; (ii) none of the studies actually detailed which interventions were suggested by the core lab to address initial signs of decompensation, or what types of interventions were implemented to manage the patients' out-of-range clinical parameters; (iii) TM relied mainly on patient-initiated communication (self-management strategies), and this may have led to an underuse of the system, particularly if the feedback was inadequate. Pulmonary artery pressure (PAP), as an invasive haemodynamic surrogate marker of filling pressure, provides a reliable vital signal that rises up to 4 weeks before HF symptom onset and hospitalization,6 being both an indicator for decompensation and a therapeutic target. As elevated values of PAP have been associated with an increased risk of death and hospitalization for HF,7, 8 the idea of remote monitoring of PAP has attracted the scientific community in the last years. Indeed, a time window of weeks would allow the physicians to intervene before clinical symptoms arise and acting a proactive way by adjusting the dose of diuretics or vasodilators. The hypothesis of a clinical role of PAP remote monitoring through a wireless implantable device has been tested firstly in the CHAMPION study,9 by using the CardioMEMS device, a small sensor capable of measuring PAP in the pulmonary artery on a daily basis. It was observed that a correct management of PAP changes caused a significant 37% reduction of HF hospitalizations in the 550 patients who implanted the device compared to the control group. An analysis of the first 2000 patients implanted with CardioMEMS after commercial release in the United States showed a greater reduction of PAPs over time compared with the CHAMPION trial,10 confirming its reliability even in a non-trial setting. One of the keys to the success of the CHAMPION study was undoubtedly the presence of precise algorithms for the evaluation and treatment of PAP changes, algorithms that have not been described in other trials with TM. Recently, the results of CHAMPION have been replicated in health systems outside the United States. The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.11 It was found that treatment modifications based on remotely monitoring of PAP were associated with fewer HF hospitalization, sustainable PAP decreases, and marked improvement of quality of life. Indeed, one could wonder whether a comprehensive platform of remote HF monitoring collecting vital signs, symptoms and PAP, possibly user-friendly for patient's engagement in his/her own monitoring, the ‘Holy Grail’ of eHealth, might play a primary role in the future for a proactive management of haemodynamic instability. In this issue of the Journal, Mullens et al.12 have addressed this challenging question and presented the first-in-human data regarding the safety and accuracy of the new Cordella™ sensor for PAP measurement and recording. In their investigation, the authors implanted the Cordella™ PAP sensor in 15 HF patients with New York Heart Association class III. Vital signs (blood pressure, heart rate, weight and oxygen saturation) and PAP data were transmitted from the patients' home to the clinical teams for proactive management of the disease. Right heart catheterization was performed as goal standard at baseline and 3-month follow-up. The primary safety endpoint was freedom from device-related adverse events for all the 30 days post-procedure and pressure sensor failure, while the primary efficacy endpoint was accuracy of the Cordella™ PAP sensor measurements compared to standard fluid-filled catheter at baseline and 90 days post-implantation. Both endpoints were met. Bland–Altman analysis demonstrated that the Cordella™ PAP sensor and fluid-filled catheter had similar variance of measurements of ±4 mmHg. Noteworthy, patient compliance was excellent, with more than 98% of patient compliance with daily measurements at 90 days. No device system-related complication, such as invasive treatment, device explant or death, occurred; the four minor adverse events resolved without sequelae. Why are these findings to be considered relevant for the future of HF management? Mainly because the Cordella HF System is a digital technology that measures, records and transmits all vital signs including PAP, but also blood pressure, heart rate, weight and oxygen saturation. This means that a measure of haemodynamic pressure is associated with clinical data, defining a complete scenario via remote monitoring which may be of great help for health care professionals in preventing HF instability and hospitalization. If causes of HF hospitalizations are analysed in detail as in the CHARM programme,13 it is evident that the measure of PAP alone cannot represent the only parameter to support a proactive intervention. Indeed, in 35% of cases, hospital admissions were not due to cardiovascular causes and included respiratory infections, anaemia, and worsening renal function, while among cardiovascular causes, 15% were due to arrhythmias, 10% to 15% to ischaemic episodes, and 10% to uncontrolled hypertension and heat rate.13 The comprehensive ideal scenario of HF monitoring is reported in Figure 1. Invasive monitoring of PAPs is associated with monitoring of vital signs and with parameters sent by the device if it has been implanted. Mobile health technologies may be integrated in this monitoring system through dedicated apps reporting data also about quality of life, symptoms and compliance to therapy.14 Are there any technical advantages of Cordella over CardioMEMS? Mullens and co-workers claim that there are several characteristics that make this technology extremely friendly for both the doctor and patient. It is easily implanted in the anterior branch of the right pulmonary artery and is equipped with radiopaque markers in order to confirm appropriate apposition. The peculiar position renders an anterior reading of the device feasible, allowing PAP measurements in a seated position and, therefore, obtaining a better compliance of the patient. For implanting physicians, the catheter tip is softer, dye can be injected through the delivery catheter allowing visualization of a more appropriate landing zone of the sensor. On top of that, the advantage of the combination of invasive and non-invasive monitoring systems providing information for the physician not available in CardioMEMS. Notwithstanding this, to correctly compare the Cordella System with CardioMEMS in terms of efficacy and safety, we should wait the publication of two trials actively enrolling, the SIRONA II (NCT03375710) and the PROACTIVE-HF (NCT04089059) trials, with longer follow-up and larger patient cohorts. Given that costs of the device and setup of the US health care system are not comparable to the European situation and several profound differences exist in the organization of HF care (HF outpatient clinic and HF nurses), the results from the CHAMPION trial cannot be translated directly to Europe. The entry into the market of a new device can only be welcome and the results of trials conducted in Europe such as Monitor-HF (CardioMEMS device), or CardioMEMS post-market study (CardioMEMS device), and SIRONA II (Cordella device) are eagerly waited. Conflict of interest: none declared.