Cardiac arrhythmias in Duchenne & Becker muscular dystrophy (BDMD)

Plain English summary of protocol

Background and study aims
This study aims to define whether minimally symptomatic disturbances of the heart rhythm occur in patients with severely weakened heart pumping function (cardiomyopathy), as part of the generalized muscle wasting conditions Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). Sudden deaths do occur in these patients but could be due to excessively fast or profoundly slow heart electrical activity or to other non-rhythm causes.

Hearts that are severely weakened from any cause become electrically unstable. This can cause very fast or very slow heart rhythms resulting in loss of heart function in pumping blood around the body. For example, sustained, very fast rhythms will present as cardiac arrest, and is the cause of most sudden deaths in patients following a heart attack. However, in dilated forms of cardiomyopathy, a similar loss of heart function can equally be caused by very slow heart rhythms. Additionally, in patients with advanced heart failure, due to stagnant blood flow in the veins can result in a major blood clot in the blood vessels of the lungs. Each of these outcomes could present similarly, a previously stable patient would become acutely unwell, lose consciousness and die within minutes. Sudden death does occur in patients with cardiac dystrophinopathy but the mechanism by which this occurs is currently unclear. This means that it is currently unknown whether, and to what extent, sudden deaths could be prevented by pacemakers or implantable defibrillator therapy.

Defining and detecting warning rhythms would for the first time allow preventative treatments to be designed and tested in patients with BMD or DMD (BDMD). Previous studies in patients after heart attacks or with comparable degrees of heart-pumping weakness due to non-BDMD forms of cardiomyopathy have shown that the occurrence of short-duration periods of unusual heart rhythms without symptoms (warning rhythms) are already known to correlate with the occurrence of lethal rhythms.

The study aims to find out how often fast or slow heart rhythms without symptoms occur in patients with BDMD and advanced reduced heart pumping function using implanted devices to record the heart rhythm. The study will also measure the size, shape, and distribution of scarring of the heart in patients or female gene-carriers, and will compare scarring between patients with BDMD and patients following a heart attack or other disease of the heart muscle who have similar heart function. The findings will help determine whether sudden deaths in patients with BDMD could be prevented by pacemaker/implantable defibrillator therapy.

Who can participate?
Adults with Duchenne or Becker muscular dystrophy (BDMD) or female BDMD-mutation carriers with similar severity of heart dysfunction.

What does the study involve?
All participants will be required to have an ECG-loop recorder implanted beneath the skin to the left side of the chest under sterile conditions and using local anaesthesia in a procedure taking about 30 min. This will typically be within two months of study entry. There are no direct connections between the device and the heart, unlike a pacemaker, these devices just record ECGs but do not provide any form of treatment.

Ideally, all patients will undergo MR-imaging of the heart on one occasion. This form of heart scanning takes about 45-60 min to complete and involves the administration of Gadolinium into an arm vein. This is to allow visualisation of scars in heart muscle. However, patients unable to undergo cMRI safely, or who are unable to tolerate the scanning process, can still be recruited to the ECG-rhythm surveillance part of the study.

The implanted loop recorder has battery life for about three years and will be programmed to detect pre-defined episodes of abnormally fast or slow heart rhythms automatically, regardless of symptoms. Participants can also record an ECG at the time of symptoms using an ‘activator’ device. Loop-recorders communicate with the hospital automatically by means of a remote monitoring system uniquely linked to each device. This allows the device to upload what it has recorded remotely and automatically via a dedicated transmitter connected to the patient’s home phone. This means that patients do not have to come to the hospital to download data and the device provides comprehensive rhythm surveillance 24 h/day. Each patient exits the study six months after the start of heart rhythm surveillance, six months after the loop-recorder implant.

Participants will be required to complete quality of life questionnaires at study entry and at six months after device implant.

Patients will have the option of having their device explanted either as they exit the study after six months or after battery depletion after about three years. Rhythm surveillance will continue to be provided through normal clinical arrangements for those who opt to keep their device beyond the six months term of this research. The loop-recorder is removed in a procedure taking about 30 min, performed under sterile conditions, and requiring local anaesthesia as the implant procedure.

What are the possible benefits and risks of participating?
There are no direct benefits to patients taking part in this research. However, some patients may benefit from knowing that their heart rhythm is being monitored continuously and that any abnormalities are being 'seen', interpreted and, when appropriate, acted upon promptly.

The only risk envisaged is the remote possibility of local subcutaneous infection at the site where the loop-recorder is implanted. As there are no connections between loop-recorders and the heart, this would be treated by device removal and a short course of antibiotic therapy. There would be minimal risk of wider sepsis. All implants will be performed by trained operators on a day case basis in a suitably aseptic environment.

Cardiac MR-imaging takes about 60 min and requires access to a vein. Some patients have very limited veinaccess due to limb contractures. Additionally, it is more difficult for adult patients with BDMD to be placed in the scanner and for them to be comfortable during imaging than for more able-bodied patients. Patients with various forms of muscular dystrophy regularly undergo and tolerate cardiac MR-imaging as part of their clinical management and staff in the Radiology Department are experienced in optimizing patient positioning and limiting their time in the scanner.

There are rare reports of patients having serious, long-term, adverse reactions following the administration of gadolinium contrast agents during MR imaging. However, this complication has been reported as occurring almost exclusively, in patients with severe renal impairment. This risk has been further minimized over recent years through changes in gadolinium formulations, dose, and administration methods.

Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
February 2018 to June 2022

Who is funding the study?
Duchenne UK (UK) and the National Institute for Health Research (UK)

Who is the main contact?
Ms Hannah Stevenson, Hannah.Stevenson2@nhs.net

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centre

Sponsor information

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN15622536_PIS_V.3.1_16Dec2020.pdf

Uploaded 29/01/2021

39425 ISRCTN results report 13.02.2023.pdf

Editorial Notes

04/04/2024: Publication reference added.
13/02/2023: A summary of results was added.
10/02/2023: The overall trial end date was changed from 31/01/2022 to 30/06/2022.
09/02/2021: Trial’s existence confirmed by the National Institute for Health Research (NIHR).