Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF): a randomised clinical trial

Summary

Background

The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system.

Methods

MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform.

Findings

Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61–75) and median ejection fraction was 30% (23–40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51–12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and –0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01–2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26–0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively.

Interpretation

Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring.

Funding

The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories.

Introduction

Heart failure is a global health problem with high mortality and morbidity and is one of the leading causes of hospital admissions.¹ As hospitals run at full capacity, one of the biggest challenges is in relocating the delivery of care from a passive hospital-centred setting towards a proactive and remote patient-centred approach for a future-proof health-care system. The evidence of telemonitoring modalities for chronic heart failure is inconsistent and limited by the multiple and heterogeneous approaches.2, 3 As haemodynamic congestion precedes overt clinical congestion,⁴ invasive parameters could provide a more adequate monitoring target. Responding to haemodynamic congestion can lead to the accurate and timely diagnosis of worsening heart failure and an opportunity for early intervention with decongestive therapies to prevent heart failure hospitalisations, often without symptoms or signs of clinical congestion. This lack of symptoms or signs is probably why many non-invasive telemonitoring modalities fail to achieve this time window because the intervention is much later in the decompensation process.2, 3, 4

The CardioMEMS-HF system (Abbott Laboratories, Abbott Park, IL, USA) measures pulmonary artery pressure as a clinically intuitive and interpretable haemodynamic parameter and surrogate estimate of left-sided filling pressure.⁴ Clinical evidence of remote monitoring with the CardioMEMS-HF system was provided by the CHAMPION trial⁵ among patients with New York Heart Association (NYHA) class III heart failure. However, the subsequent GUIDE-HF trial⁶ that aimed to test a broader patient population with NYHA class II–IV heart failure and either increased N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations or hospitalisation was inconclusive. The study was debated in a mostly statistical discussion and left the field with several questions. First, both trials were done in North America (predominantly in the USA, with a few sites in Canada). The value of pulmonary artery pressure monitoring in other health-care systems remains unknown, as the USA has a different health-care system, with a relatively lower adherence to guideline treatment but a higher rate of device implantation compared with western European countries, and a health-care structure different to those of most European countries.7, 8, 9 Second, GUIDE-HF was partially done during the COVID-19 pandemic, the follow-up was short and fixed at 12 months, and the control group received telephone calls at least once every 2 weeks, leaving several remaining questions.⁶ Although some post-marketing approval studies confirmed the safety of the procedure and the reduction in heart failure hospitalisations with historical controls,10, 11 the aggregated trial evidence until now has resulted in a weak or uncertain recommendation for the CardioMEMS-HF system in the American Heart Association/American College of Cardiology 2022 and European Society of Cardiology 2021 heart failure guidelines: class IIb12, 13

Research in context

Evidence before this study

We searched PubMed for articles published in English and completed trials registered on ClinicalTrials.gov up to April 1, 2023, with the search terms “heart failure”, “pulmonary artery pressure sensor”, and “randomised clinical trial”. Our search identified two previous randomised trials (CHAMPION and GUIDE-HF). The CHAMPION trial randomly assigned 550 patients with New York Heart Association (NYHA) class III heart failure and previous heart failure hospitalisation irrespective of ejection fraction and showed a significant 28% reduction in heart failure hospitalisation at 6 months. The study was not powered for mortality. The GUIDE-HF trial included 1000 patients with NYHA class II–IV heart failure and increased N-terminal pro-B natriuretic peptide (NT-proBNP) concentrations or previous heart failure hospitalisation to broaden the range of eligible patients. The overall result was neutral but a prespecified COVID-19 analysis showed a significant benefit in reducing heart failure hospitalisation. The results of GUIDE-HF might have been related to the selected population having relatively low risk (mean ejection fraction of 40%, low pulmonary artery pressure, and NYHA class II) or additionally, by modification of the COVID-19 interaction. To date, no randomised data are available after the GUIDE-HF trial. Furthermore, trial data from a different health-care system other than that of the USA are absent, including data from trials with open-label access or comparison with a standard of care control group. As the current recommendation in the European Society of Cardiology heart failure guideline is for class IIb and pulmonary artery monitoring is not reimbursed, this has resulted in minimal uptake in Europe, so far, according to these aggregate data.

Added value of this study

Heart failure hospitalisations and mortality remain high among patients with heart failure. The MONITOR-HF trial is the first randomised clinical trial to investigate the benefits of pulmonary-artery-pressure-guided management in a European health-care system. Significant differences exist between Europe and the USA that are related to governance, financial and reimbursement strategies, as well as patient factors such as health-care insurance status and health-care access, and thresholds of hospital care availability. Studying a different health-care system in addition to this single technology is thus of direct importance and can answer several remaining questions for regulatory agencies and payers. The Netherlands is known for its high quality of care, as exemplified by a comparison of the US CHAMP-HF and Dutch CHECK-HF registries. The MONITOR-HF trial showed an appropriate level of contemporary guideline-directed-medical-therapy with high uptake of angiotensin receptor–neprilysin inhibitors and SGLT2-inhibitors. Additionally, this study provided detailed information about medication changes and natriuretic peptide concentrations from baseline to follow-up, elements that were lacking in previous trials that are important to study the effect of the intervention. This trial provides novel data with respect to quality of life of patients and heart failure hospitalisations.

Implications of all the available evidence

The findings of MONITOR-HF showed a consistent benefit of haemodynamic-guided care for patients with heart failure by substantially improving quality of life and reducing heart failure hospitalisations. The additive evidence of haemodynamic monitoring in addition to standard care in the Netherlands is also of interest for other European countries. The aggregate evidence from the three trials could affect guideline recommendations on the use of haemodynamic-guided management with pulmonary artery sensors and subsequent reimbursement programmes throughout Europe and beyond.

Therefore, there is a need for randomised trial data with additional geographical diversity as well as a call for an open-label trial using an actual standard of care control group to test another health-care system rather than a single technology¹⁴ Such data might shift the balance of aggregate evidence.

The MONITOR-HF randomised clinical trial investigated the effectiveness of remote haemodynamic monitoring in addition to standard care following contemporary treatment guidelines on quality of life (QOL) and heart failure hospitalisations in the Netherlands.¹⁵