Elsevier

The Lancet

Volume 387, Issue 10017, 30 January–5 February 2016, Pages 453-461
The Lancet

Articles
Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial

https://doi.org/10.1016/S0140-6736(15)00723-0Get rights and content

Summary

Background

In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group.

Methods

The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661.

Findings

Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55–0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40–0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported.

Interpretation

Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure.

Funding

St Jude Medical Inc.

Introduction

Heart failure is a complex clinical syndrome and a global public health problem affecting an estimated 26 million people worldwide.1 Despite increased use of pharmacological2, 3, 4, 5, 6, 7, 8, 9 and device therapy options10, 11, 12, 13 shown to significantly improve clinical outcomes in randomised controlled trials, morbidity and mortality in heart failure remain a major burden to patients, caregivers, and national health-care systems.14, 15 The incidence of hospital admissions for heart failure is also high with more than 1 million admissions per year in the USA.16, 17

Heart failure will become even more prevalent in the next 15 years and US health-care costs are projected to increase from US$31 billion in 2012 to $70 billion in 2030.18 New management strategies are needed and should be based on the underlying pathophysiology of heart failure decompensation. One such strategy, haemodynamic-guided medical management, improves outcomes in selected patients with both reduced and preserved ejection fraction. This approach provides actionable information to physicians in an efficient manner and helps to improve the treatment decision making processes of disease management.19

Research in context

Evidence before this study

We searched PubMed and the Cochrane Library on July 6, 2015, with the search terms “haemodynamic [or hemodynamic] monitoring [or monitor]” and “heart failure”. Trials considered important included multicentre, randomised, controlled designs in patients with heart failure using implantable lead-based systems in the right ventricular outflow tract and implantable wireless systems in the pulmonary artery for ambulatory patient management, as well as pulmonary artery catheter assessment for acute patient management. We also found an ongoing multicentre, randomised, controlled implantable device trial using a lead-based system in the left atrium. Several small, open-label clinical investigations with short study durations of various implantable device systems were reviewed, but were unable to provide meaningful insights regarding long-term clinical benefits of these technologies in managing heart failure. A comprehensive Cochrane review of telemonitoring programmes for patients with chronic heart failure has been published that suggests the potential for long-term clinical benefit; however, few studies of haemodynamic monitoring were included in the review, which restricts its interpretation and direct application to the current dataset.

Added value of this study

Previous evidence has shown that haemodynamic-guided management of heart failure significantly reduced admissions to hospital after 6 months of testing. This study provides complete follow-up results from the CHAMPION trial showing sustained efficacy of haemodynamic-guided management of heart failure to reduce admissions to hospital, both during a randomised clinical trial setting, as well as in a follow-up setting more typical of clinical practice. Additionally, the combined risk of death or admission to hospital for heart failure was significantly reduced with a favourable trend towards a reduction in mortality. These data from 31 months of follow-up represent the longest follow-up of the effect of haemodynamic care ever reported.

Implications of all the available evidence

This study reports new findings that patients with chronic heart failure who are managed with pulmonary artery pressure information transmitted from an implantable device not only have better short-term clinical outcomes but also have significantly better long-term clinical outcomes than patients receiving guideline-directed standard of care management alone.

The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association (NYHA) Class III Heart Failure Patients (CHAMPION) trial (ClinicalTrials.gov, NCT00531661) tested the hypothesis that pulmonary artery pressure guided heart failure management with a wireless implantable haemodynamic monitoring system (CardioMEMS™ Heart Failure System, St Jude Medical Inc, Atlanta, GA, USA) would be a superior way to reduce hospital admissions for heart failure compared with usual guideline-directed medical management alone.21 The CHAMPION trial met all primary efficacy, safety, and secondary endpoints22 with positive results in the prespecified subgroup analysis involving patients with preserved ejection fraction heart failure23 as well as other important subgroups.24, 25, 26 The primary endpoint of CHAMPION, rate of hospital admissions for heart failure, was assessed at 6 months during which pulmonary artery pressure guided management group (treatment group) had a significant 28% reduction (0·32 events per 6 months vs 0·44 events per 6 months).

We examine the extended efficacy of this strategy over an 18-month randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months.

Section snippets

Study design and participants

The design of the CHAMPION study has been described previously.20 Briefly, the CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with NYHA Class III heart failure symptoms and a previous admission to hospital. All patients initially underwent right heart catheterisation with haemodynamic assessment and implantation of the pulmonary artery pressure sensor20, 22, 23, 24, 25, 26, 27, 28, 29 before randomisation. Patients with NYHA Class III

Results

Between Sept 6, 2007, and Oct 7, 2009, 575 patients met the clinical inclusion/exclusion criteria, provided written informed consent, and underwent the right heart catheterisation procedure, 25 patients did not receive a device implant and were not randomised (figure 1), leaving 550 patients who were implanted with the device and randomly assigned to either the treatment group (n=270) or to the control group (n=280). Patient baseline demographic and clinical characteristics were well balanced

Discussion

Haemodynamic-guided care for symptomatic patients previously admitted to hospital maintains clinical stability and avoids decompensation leading to hospital admission.22, 23, 24, 25, 26 This approach was superior to relying only on standard disease management strategies of monitoring weights and symptoms, as was done in the control group of the trial. Results of the CHAMPION trial are consistent with hypothesis-generating observations from previous underpowered trials of implantable

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