Non-invasive Detection of Coronary Artery Stenosis

The aim of this viability study is to investigate using a novel medical device, the potential for detecting partial blockages in the arteries within the wall of the heart (coronary artery stenosis). A prototype device will be used in the proposed study. It is a stick-on patch containing sensors which measure the vibration produced at the chest surface by flowing blood as it accelerates through the narrowed artery in the heart emerging downstream, hitting the inner wall of the artery and causing it to vibrate. Some of the energy in the vibrations reaches the skin of the chest, allowing the blockage to be detected non-invasively. The principle has been proved in the laboratory using a simple chest model but to date no measurements have been made in people. Therefore, the proposed trial will serve as the first in-human measurements and will involve a small number of patients and healthy volunteers, with the objective of establishing if it is possible to determine the presence or absence of the stenosis.

The patch will be tested by recording acoustic signatures in healthy volunteers, then in patients undergoing coronary CT angiography. Results will be validated against the CT angiography gold standard. At this early stage no clinical decisions will be made based on the patch recordings and the data will be used only to assess the feasibility of continuing the development of the device.

This feasibility study is a non-randomised, proof of concept study being undertaken at a single clinical centre. It involves a novel, non-invasive battery powered medical device that is not CE marked. As a non-CE marked device, review and approval of the proposed clinical investigation a UK Competent Authority, the HRA, is required in addition to ethical review and approval.

The device, a patch containing microphones and accelerometers applied to the chest, is battery powered and will not introduce any energy or substances into the subjects involved in the study. The device will listen for sounds and movement within the body of the individual being examined. The signals detected by the microphones and accelerometers are transmitted wirelessly to a data acquisition unit which is connected to a laptop computer more than 2 metres away from the patient, which displays the signals in real time and stores them for later analysis off-line.

Data (acoustic signatures) will be collected from patients with known or suspected coronary artery disease. Results will be compared with the current gold standard of coronary angiography or coronary CT angiography.

The risk to participants is minimal. No specific risks associated with the use of the device have been identified and no requirement for additional testing has been identified. There are no anticipated interactions with concomitant medical treatments.

The results of this study will not be used to manage the treatment pathway of the patient involved.

If proof of concept is successfully demonstrated with the new device, a larger randomised study will be undertaken to obtain the clinical data necessary to support commercial and regulatory requirements.

Having conducted in-vitro proof of principle experiments (as listed in the references section) and before conducting a formal validation trial, we wish to determine the viability of the new patch device in an initial study on a small number of patients undergoing coronary angiography. We aim firstly, to prove the principle that it is possible to distinguish between those with and those without coronary artery stenosis and, secondly to assess how well the device is tolerated by the patient and how easy it is to deploy the patch and take readings 'in the field'. We believe that this small trial is essential to provide first in human data to support applications for funding a larger validation trial.

Potential study participants will be recruited from patients attending, the Cleveland Clinic who have agreed to elective angiography or CTa investigation. All potential participants will be screened against the inclusion and exclusion criteria detailed elsewhere. This is a non-randomised study. Accordingly, participants will be recruited i on a sequential basis until a total sample size of at least 20 is reached.

Written Informed Consent will be obtained from all participants before recruitment into the study and this will be recorded on the consent form. The nature of the measurements and the nature of the clinical investigation, together with all procedures and risks will be fully explained to each prospective participant by one of the Investigators or members of the research team. If the patient meets all inclusion/exclusion criteria and agrees to participate in the study, he/she will be invited to sign the approved CF.

When the potential subject has agreed to take part, they will undergo the following procedures (approximate times in brackets).

* Height, weight and blood pressure recording. (15 minutes)
* CTa or angiography scan as normal. (30 minutes)
* Patch attached and wireless connection to remote receiver established.
* The patch will be adjusted to ensure that the patient is comfortable
* Data recorded. (15 minutes)
* Patch removed. (5 minutes)
* Subject asked to suggest any aspects of the procedure that might be improved. All comments noted. (10 minutes)

The patch data will be analysed blind by a member of our team who would not take part in the recording sessions. For the analysis the time series data will be transformed to the frequency domain and the relative acoustic power detected by each sensor over various frequency range will be tabulated. For this small preliminary study, the agreement between the reference and test method to determine the categorical variable namely, the presence or absence of a coronary artery stenosis, will be assessed by Cohen's Kappa test. This measures how much the agreement between the two methods exceeds what would be expected by chance. At this early stage no further statistical tests are planned.

Eligibility Criteria:
Inclusion Criteria:

1. Patient is able to provide written informed consent
2. Age ≥18 years;
3. Investigation for suspected stable coronary artery disease/stenosis isolated from other cardiac comorbidities.
4. Subjects of either sex. Female subjects of child-bearing potential will be included if deemed suitable for clinically mandated coronary CTa.
5. No infectious disease or neoplasia.

Exclusion Criteria:

1. Indications to coronary CTa different from isolated suspected stable coronary artery disease, such as acute coronary syndrome, unstable angina, congenital heart disease, cardiomyopathy, heart valve disease, aortic coarctation, electrophysiological disorder/arrhythmia, screening study, unstable clinical condition, left ventricular ejection fraction \<35%, previous coronary revascularization (PCI or CABG surgery), previous heart valve surgery or transcatheter valve replacement, pace maker or implantable defibrillator.
2. If female and of child-bearing potential: evidence of a positive pregnancy test or a stated intention to become pregnant in the next 6-12 months;
3. Currently participating in another device or drug study or has done so in previous 3 months.