Assessment of Cardiac Function Using Combined Cardiovascular Magnetic Resonance and Cardiopulmonary Exercise Testing (CMR-CPET) (CMR-CPET)

What problems limit patients' response to exercise? Using exercise cardiac magnetic resonance imaging to assess the heart's response, with simultaneous measurement of respiratory oxygen and carbon dioxide levels to assess the lung and skeletal muscle responses, to identify the rate-limiting factors affecting different types of patient

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Procedure: Combined Cardiovascular Magnetic Resonance and Cardiopulmonary Exercise Testing

Detailed Description

Background and study aims Many medical conditions that affect the heart and lungs can cause breathlessness. People affected by breathlessness often require a number of tests to diagnose the medical condition responsible for their symptoms.

Cardiac MRI (magnetic resonance) scanning is already used to help diagnose and monitor patients with heart conditions (for example cardiomyopathy and pulmonary hypertension). By exercising while having an MRI scan, and at the same time measuring the gases breathed in and out from the air, it will be possible to more accurately understand the changes that occur in the heart, lungs and muscles.

The purpose of this study is to develop our understanding of the cardiovascular response to exercise in patients with non-ischaemic cardiomyopathy.

Who can participate? Patients aged 18 - 80 years with symptoms of breathlessness on exertion, and under the care of cardiology, pulmonary hypertension or rheumatology clinics for non-ischaemic cardiovascular disease.

What does the study involve? Participants will be invited to an appointment at the cardiovascular MRI department at the Royal Free Hospital. On the day of the appointment, participants will be welcomed to the department by the research team and the researchers will check that participants are well enough to exercise and safe to have an MRI scan. There will be an opportunity to ask any further questions.

The researchers will ask participants to perform exercise in one of three ways:

1. Using our special MRI safe exercise bike: The researchers will show participants how to use this and then the researchers will help participants to get on it and into the MRI scanner.
2. Lifting a weight using their arms: The researchers will check how much weight participants would be expected to manage before participants enter the scanner. The researchers will ask participants to lift and hold a weight using their dominant arm during the scan.
3. Stepping one (or both) leg(s) using an elastic resistance band. The researchers will measure the band so it is of the appropriate length for participants, and the researchers will show participants how to perform the exercise when in the scanner.

The researchers will give participants a special face mask to wear to measure the concentration of gases in exhaled breath (like carbon dioxide or oxygen) and breathing volumes. Most adults and children find the face mask comfortable and easy to wear.

The researchers will give participants a head-set so that participants can communicate at all times with the person running the scan.

First participants will have a MRI scan where the researchers ask participants to lie back and relax (this will take about 30 minutes).

Then the researchers will ask participants to exercise on the MRI safe bike for about 7 minutes, lift the weight for about 3 minutes, or perform leg stepping for about 3 minutes whilst participants are having continuous MRI scanning.

After the scan, the researchers will help participants out of the scanner.

What are the possible benefits and risks of participating? There are no individual benefits to taking part. The researchers hope that information from this study will help improve the understanding and treatment of heart conditions that can limit exercise ability. If participants like the researchers can make participants a copy of their scan on CD to keep. Sometimes the researchers might find new information that the researchers need to tell their treating doctor straight away. If the researchers do find such information the researchers will let participants and their doctor know as soon as possible. The researchers will reimburse reasonable travel expenses for participants to attend the research scan (unless participants are already scheduled to have a clinical visit on the same day). MRI scanning is very safe.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Hospital NHS Foundation Trust
    • Contact: James Brown; Phone Number: +44 (0)2074332780; Email: james.brown1@nhs.net
    • Principal Investigator: Daniel Knight

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 - 80 years with symptoms of breathlessness on exertion, and under the care of cardiology, pulmonary hypertension or rheumatology clinics for non-ischaemic cardiovascular disease.

Description

Inclusion Criteria:

1. Age 18-80 years
2. Symptoms of breathlessness on exertion under the care of cardiology, pulmonary hypertension or rheumatology clinics for non-ischaemic cardiovascular disease
3. Willing and able to provide written informed consent

Exclusion Criteria:

1. Previous ischaemic heart disease (including angina, myocardial infarction, PCI, CABG)
2. Unstable symptoms (including crescendo angina or angina at rest, and syncope on exercise)*
3. Arrhythmia**
4. Musculoskeletal disease preventing exercise
5. Patients unable to provide consent
6. General contraindications to CMR (e.g. implanted metal objects, pregnancy, severe claustrophobia)
7. Significant parenchymal lung disease (defined as >20% extent parenchymal disease on CT)
8. WHO functional class IV symptoms *Patients with unstable symptoms have been excluded as it would be unsafe for them to perform exercise whilst in a MRI scanner. Patients unable to exercise, WHO functional class IV and those with significant lung disease have been excluded as they would be unable to complete the exercise protocol **The researchers have excluded patients with arrhythmia as this can reduce the reliability of some of the CMR image sequences and also results in less predictable heart rate response to exercise

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output (L/min) measured using aortic flow from PCMR measurements	Cardiac output (L/min) measured using aortic flow from PCMR measurements measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Ventricular volumes (mL) measured using volumetric measurements of both ventricles, at end-diastole and end-systole	Ventricular volumes (mL) measured using volumetric measurements of both ventricles, at end-diastole and end-systole measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Heart rate (bpm) from MRI ECG/heart rate monitor	Heart rate (bpm) from MRI ECG/heart rate monitor measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Blood pressure (mmHg) from MRI-compatible BP monitor	Blood pressure (mmHg) from MRI-compatible BP monitor measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Oxygen consumption (VO2, mL/min) from CPET machine	Oxygen consumption (VO2, mL/min) from CPET machine measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Carbon dioxide production (VCO2, mL/min) from CPET machine	Carbon dioxide production (VCO2, mL/min) from CPET machine measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Arteriovenous Oxygen Gradient (Muscle oxygen consumption, mlO2/100mL blood/min) calculated from Cardiac Output and VO2	Arteriovenous Oxygen Gradient (Muscle oxygen consumption, mlO2/100mL blood/min) measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise calculated from Cardiac Output and VO2	Change from Baseline at 3 months
Respiratory exchange ratio (RER) from CPET machine	Respiratory exchange ratio (RER) from CPET machine measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months
Exercise duration (sec) measured using a timer from the start to the end of exercise	Exercise duration (sec) measured using a timer from the start to the end of exercise measured at rest, at 2 minutes intervals during exercise, at 2 minutes and 4 minutes after end of exercise	Change from Baseline at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Troponin T (ng/L) measured using blood sample prior to scan	Cardiac Troponin T (ng/L) measured using blood sample prior to scan and after scan	through study completion, an average of 1 year
N-terminal pro-BNP (ng/L) measured using blood sample prior to scan	N-terminal pro-BNP (ng/L) measured using blood sample prior to scan and after scan	through study completion, an average of 1 year
Haemoglobin (g/L) measured using blood sample prior to scan	Haemoglobin (g/L) measured using blood sample prior to scan and after scan	through study completion, an average of 1 year
Autoantibody profile measured using blood sample prior to scan	Autoantibody profile measured using blood sample prior to scan and after scan	through study completion, an average of 1 year
Invasive pulmonary pressures (PA systolic/diastolic/mean) in MR-RHC substudy measured using a pressure transducer at rest and after 1 min of exercise	Invasive pulmonary pressures (PA systolic/diastolic/mean) in MR-RHC substudy measured using a pressure transducer at rest and after 1 min of exercise	through study completion, an average of 1 year
PH disease progression (WHO Functional class) measured using patient records	PH disease progression (WHO Functional class) measured using patient records	Change from baseline at 6 months
Mortality measured using patient records	Mortality measured using patient records	Change from baseline at 6 months

Collaborators and Investigators

• Sponsor: Royal Free Hospital NHS Foundation Trust
• Collaborators: British Heart Foundation; Actelion

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: July 12, 2020
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 100358; 226101 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data generated or analysed during this study will be included in the subsequent results publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No