CROSS sectional versus invasive imaging in patients with Heart Failure (CROSS-HF)

The trial

The aim of this trial is to establish if it is possible to reduce the need for invasive angiography in patients with newly diagnosed heart failure.  3000 patients presenting with a new diagnosis of heart failure and not known to have coronary artery disease will be recruited. They will be randomly assigned (equal chance) to one of three tests: 

1. Invasive coronary angiogram (current NHS practice)- A specialised X-ray test where dye is injected directly into the heart arteries via the groin or wrist. It carries a small risk of serious complications such as stroke. The test exposes patients to radiation and is expensive (NHS tariff up to £1563). Furthermore, there are long waiting lists for the test following many cancellations due to the COVID-19 pandemic. 

2. CT coronary angiography - this test is quick, non-invasive and cheaper than invasive angiography (NHS tariff up to £310). It has a high accuracy for detection of coronary artery disease but can be challenging in certain patient groups such as elderly patients or those with irregular heart rhythms. It also exposes patients to a small dose of ionising radiation. 

3. Stress cardiovascular MRI - This test is non-invasive and cheaper than invasive angiography (NHS tariff up to £596) and provides additional information on the structure and function of the heart. The accuracy of this test for detection of coronary artery disease is unproven in patients with heart failure. It does not expose patients to ionising radiation. 

We will maximise recruitment of patients who have been poorly represented in heart failure trials: including elderly, ethnic minority and socio-economically disadvantaged patients. We will reduce barriers to participation and work with the NIHR ethnic minority research inclusivity group to develop a YouTube video explaining the rationale of the trial and the importance of participation. The video will be in plain language and will be available in a variety of languages.  

We have designed the trial to minimise inconvenience to patients without any additional hospital visits. All follow up will be done remotely mainly by review of electronic health records. Surveys to explore patient experience will be sent out online, by text message or post according to patient preference. We will work out whether these tests are good value for money for the NHS.   

Dr Peter Swoboda

Associate Professor in Cardiology

Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, LS2 9JT

Email: P.Swoboda@leeds.ac.uk

Professor John Greenwood

Honorary Professor of Cardiology

Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, LS2 9JT

Email: j.greenwood@leeds.ac.uk

Professor Colin Berry

Professor of Cardiology and Imaging

School of Cardiovascular and Metabolic Health, BHF Glasgow Cardiovascular Research Centre, 126 University Place, University of Glasgow, G12 8TA

Email: colin.berry@glasgow.ac.uk

Professor Mark Petrie

Professor of Cardiology

Institute of C&MS, BHF GCRC, University of Glasgow, G12 8TA

Email: mark.petrie@glasgow.ac.uk

Professor Gerald McCann

NIHR Research Professor and Professor of Cardiac Imaging

Department of Cardiovascular Sciences, University Rd, University of Leicester, LE1 7RH

Email: gpm12@leicester.ac.uk

Professor Iain Squire

Professor of Cardiology

Department of Cardiovascular Sciences, University Rd, University of Leicester, LE1 7RH

Email: is11@leicester.ac.uk

Dr Jonathan Weir McCall

Department of Radiology, School of Clinical Medicine, University of Cambridge, CB2 0SP

Email: jw2079@cam.ac.uk

Health Economics

Robert Heggie

Research Associate

School of Health & Wellbeing, Clarice Pears Building, 90 Byres Rd, University of Glasgow, G12 8TB

Email: robert.heggie@glasgow.ac.uk

Professor Olivia Wu

William R Lindsay Chair of Health Economics

School of Health & Wellbeing, Clarice Pears Building, 90 Byres Rd, University of Glasgow, G12 8TB

Email: olivia.wu@glasgow.ac.uk

Charity Partner

Cardiomyopathy UK

Trial summary

Trial title

CROSS sectional versus invasive imaging in patients with Heart Failure (CROSS-HF)

Aim

To establish whether, in patients with heart failure, a strategy of non-invasive imaging with computed tomography coronary angiography (CTCA) or stress cardiovascular magnetic resonance (CMR) is non-inferior to invasive coronary angiography (ICA) in terms of major adverse cardiovascular events (MACE), patient reported outcome measures, and cost-effectiveness.

Trial Design

Multicentre, open-label randomised controlled trial with patients randomised 1:1:1 ratio to ICA, CTCA and stress CMR

Primary Outcome

Time to first MACE measured from randomisation for a minimum of 12 months:

MACE defined as any of:

• All cause death
• Myocardial Infarction (MI)
• Heart Failure Hospitalisation

Secondary Outcome

• Total MACE events (MACE is defined as all-cause mortality, MI and heart failure hospitalisations)
• Total (first and recurrent) HF hospitalisations
• KCCQ-CSS at 6 and 12 months
• Total Cardiovascular (CV) deaths
• Total all-cause mortality

Inclusion Criteria

1. Onset of symptoms ± signs of heart failure in past 12 months AND

2a. Non-elective heart failure hospitalisation (where heart failure was the primary reason for hospitalisation in the opinion of the investigator) OR

2b. Outpatients with LVEF ≤40% OR

2c.  Outpatients with LVEF >40% and NT-proBNP >300ng/L (sinus rhythm) or >600ng/L (AF)

Major Exclusion Criteria

• Previous investigations for coronary artery disease (CAD), where CAD was identified as the cause of heart failure
• Clear alternative cause of heart failure (e.g. cardiac amyloidosis or hypertrophic cardiomyopathy)
• Severe valvular heart disease thought to be the main cause of heart failure
• Comorbid conditions with lifespan of less than a year (in the opinion of the investigator)

Sample Size and Enrolment

• N=3000
• Expected set up start date 1^st April 2024
• Expected first patient recruited by 1^st October 2024
• Expected pilot phase completed by 1^st July 2025 (9 months from opening)
• Expected last patient recruited by 1^st April 2028
• Expected last follow up assessment 1^st April 2029
• At least 20 sites recruiting 5 patients per month

Flow chart

 

LAY SUMMARY

Each year in the UK at least 60,000 patients are diagnosed with heart failure. Coronary artery disease (narrowing of the blood vessels supplying the heart) is the most common cause of heart failure. It is important to identify coronary artery disease because these patients have increased risk of dying and may respond less well to modern treatments. Invasive coronary angiography (described below) is often done as the first line test to identify coronary artery disease in a fifth of patients with heart failure in the UK. However, we know from work with our patient and public involvement groups and patient charities (including British Society for Heart Failure Patient Group and Cardiomyopathy UK) that most patients would prefer to avoid invasive coronary angiography if possible.

The aim of this trial is to establish if it is possible to reduce the need for invasive angiography in patients with newly diagnosed heart failure. 3000 patients presenting with a new diagnosis of heart failure and not known to have coronary artery disease will be recruited. They will be randomly assigned (equal chance) to one of three tests:

1. Invasive coronary angiogram (current NHS practice)- A specialised X-ray test where dye is injected directly into the heart arteries via the groin or wrist. It carries a small risk of serious complications such as stroke. The test exposes patients to radiation and is expensive (NHS tariff up to £1563). Furthermore, there are long waiting lists for the test following many cancellations due to the COVID-19 pandemic.

2. CT coronary angiography - this test is quick, non-invasive and cheaper than invasive angiography (NHS tariff up to £310). It has a high accuracy for detection of coronary artery disease but can be challenging in certain patient groups such as elderly patients or those with irregular heart rhythms. It also exposes patients to a small dose of ionising radiation.

3. Stress cardiovascular MRI - This test is non-invasive and cheaper than invasive angiography (NHS tariff up to £596) and provides additional information on the structure and function of the heart. The accuracy of this test for detection of coronary artery disease is unproven in patients with heart failure. It does not expose patients to ionising radiation.

We will maximise recruitment of patients who have been poorly represented in heart failure trials: including elderly, ethnic minority and socio-economically disadvantaged patients. We will reduce barriers to participation and work with the NIHR ethnic minority research inclusivity group to develop a YouTube video explaining the rationale of the trial and the importance of participation. The video will be in plain language and will be available in a variety of languages.

We have designed the trial to minimise inconvenience to patients without any additional hospital visits. All follow up will be done remotely mainly by review of electronic health records. Surveys to explore patient experience will be sent out online, by text message or post according to patient preference. We will work out whether these tests are good value for money for the NHS.

If this trial shows that non-invasive imaging tests are no worse than invasive angiography then we will be able to reduce the thousands that are done each year in the NHS. We hope this will lead to improved patient experience and cost savings without affecting the health of patients with heart failure.

Links

Cardiomyopathy
https://www.cardiomyopathy.org/

British Society for Heart Failure
https://www.bsh.org.uk/