FEASIBILITY OF IMPROVING RISK STRATIFICATION IN BRUGADA SYNDROME
Research type
Research Study
Full title
FEASIBILITY OF IMPROVING RISK STRATIFICATION IN BRUGADA SYNDROME
IRAS ID
223181
Contact name
P Kanagaratnam
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary:
Brugada syndrome is an inherited heart condition. Most people who have it are unaware of any problems relating to it. Unfortunately, a small number of people with the condition can suddenly develop a dangerous fast heart beat that can lead to death. There is no cure, but implanting a cardioverter-defibrillator (ICD), which is like a pacemaker can save the life of affected individuals. However, ICD implantation has its own problems, so choosing who gets an ICD is a very important decision.The current approach to selecting people for an ICD is not very effective and a better method is needed. We have developed a new technique called the Cardiac Conduction Stability Test. This involves wearing a special vest which records electrical signals, and running on a treadmill. We have used it to identify abnormalities in the hearts of people with Brugada Syndrome who have also survived a life-threatening event.
We would like to expand the use of this test to understand if it can be effective in identifying patients who should have an ICD.
Summary of Research:
141 people took part in our studies – ranging from people with a family history of cardiac conditions to those surviving cardiac arrest. Each volunteer performed an exercise test with a state-of-the-art electrical sensor vest and underwent a 3D X-ray scan (computerized tomography, CT) of the chest. Volunteers also kindly provided us with their personal and family history as well as clinic investigations to help us make sense of the data we collected. One patient had a fast abnormal heart rhythm after exercise, but this resolved after less than a minute of resting without any significant symptoms or medical intervention. We expected to find problems in the lungs from CT scans unrelated to our study – this happened in five patients who all received a referral to the relevant expert at our centre.
We discovered several new aspects of our field from the data:The electrical recovery patterns of the heart change with exercise differently if you have survived a cardiac arrest. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbSu94g-2Fw7XUVx4K3PFSk7eu-2Fj7RgW-2F2zCt5y7glUSzUJYn8K_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI4sgJeu3h-2BtoWiMWUtidIFdEBtXRGtrcgjUZgZcifxnJNvyJ4WOR6UCPA76Icz5v9dGRXhitRbGDXoiken0al1nhk0apr2hglQ8OC8n-2BJE3XPb0J7oO39r49rAbRQLhmncFQgfHEOJT4VWv96fbFuZNKY7PcDSBRbktwoD-2BQMy6g-3D-3D&data=05%7C01%7Cfulham.rec%40hra.nhs.uk%7C792e816d951f4b29fc3308dbac481d4f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638293197949406377%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=Dzp%2FMKoU8jcZ5jNN024OJoYu39ObEff%2Fd%2Bunn%2Fkyo6U%3D&reserved=0
Stability of electrical patterns of the heart can be measured and given a score out of 100 – our group created the software to make this possible and named it Ventricular Conduction Stability (V-CoS). https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbYmQsGrKhqntA-2FbTU5g6kdGA4mzJWSntSm75v4tbQACe9J_X_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI4sgJeu3h-2BtoWiMWUtidIFkNhnodAaSFFijL9kIA2ENVztuTTqZPRXxWc0-2FULKUUG8KpT4cdrXSD4qCjzq2dg2WYzxX9oldiVJLyMUb5UX8qw-2BH1xvZWueX4l2nX97US9FPfAXogpSTZhIPlZzdvkNGyFI5aA540la1Y-2Bmgk-2Fr0g-3D-3D&data=05%7C01%7Cfulham.rec%40hra.nhs.uk%7C792e816d951f4b29fc3308dbac481d4f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638293197949406377%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=Zv%2FKY%2BmXDtcOEYkxqk9NSn2PpAOkTCGX3KLzS5C83d0%3D&reserved=0
This V-CoS test can successfully tell the difference between cardiac arrest survivors and patients who have not experienced such lethal arrhythmia even when all other cardiac tests are normal. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbYmQsGrKhqntA-2FbTU5g6kdHPbTRRCjDbK-2B1In0bxBgVWFBqzAse-2BN-2BsPyaMNMMd5EQ-3D-3DPav__E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI4sgJeu3h-2BtoWiMWUtidIFpoTTZewP088LLg0a0YzTCqLORKrGI68shAxMiDRprUQmDi2SLj1GFDcXNU8g3GbSEOz7axsZkM3Nqpu-2Fp-2F7GjSOeAo1XoCNeNL66FZCPFIiShCmQJoM8wnwfi4cCG-2FpbAhuN4EjqpmTNY72CLDBjGw-3D-3D&data=05%7C01%7Cfulham.rec%40hra.nhs.uk%7C792e816d951f4b29fc3308dbac481d4f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638293197949406377%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=cu%2FmOZMPsyh8et%2BWj0qXx7n0xvhFKmvfPSC7jrauDos%3D&reserved=0
Performing the V-CoS test repeatedly shows that there is a regular pulsation in electrical changes after exercise that is seen in cardiac arrest survivors. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbbdJugJLCLZfQYimqdLU2ypjWBvFUJgwau1CRdOHJ2P-2FEAAaVX2rTGOu1B0mk3bHwL7VPpW7GA7OO-2Bmj0TPhUkc-3DChDj_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI4sgJeu3h-2BtoWiMWUtidIF7lsZGjQYy0fBeFfc-2F9Cj1zOAM9LTEyFVX2KSXp6KwZtwfvAKhpEJPDEf9aE05tVoJNRAIGw8yNhlfll6L1OWm4eQS3q6aj-2BqdKzzuQFUfwc4fgsWaC9OG-2BzkINk-2FEO-2FyXiTWD81S-2BjOXTBLEKap1jg-3D-3D&data=05%7C01%7Cfulham.rec%40hra.nhs.uk%7C792e816d951f4b29fc3308dbac481d4f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638293197949406377%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=FuAqFd%2FWn0IHY9vy09gSq%2FKdzaekEPcSlaNyMJ4kQlg%3D&reserved=0 page S466.
The V-CoS test can tell the difference between Brugada syndrome patients and their unaffected relatives even when the standard ECG heart tracing is apparently normal. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbfc0AJp3txhrRMgW2idGNToCAzMfhGGqDV0GMCs9741rz1H6mjxsN37j5YcYXPVrbA-3D-3D4290_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI4sgJeu3h-2BtoWiMWUtidIF4I1Tgflx21WbPwer1VASwFLT5AYVyBkW55EoxmasQorsYb21q6BvicJIiOUlzlU9lthmdyyorgSfpKABNs8KxbYj0bToMy7FonmQ0Pf3j3Px0bN7ywnhfitLtXZgOZ1-2Bu1PvJKUOfrjEJB-2FOfhPdHw-3D-3D&data=05%7C01%7Cfulham.rec%40hra.nhs.uk%7C792e816d951f4b29fc3308dbac481d4f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638293197949406377%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=Cd1%2F5Vj3hyPikV6Kbsm681BJ4PX94bJRhBWTw5ifZMI%3D&reserved=0 Abstract 07-17
Other electrical measurements can be combined to pick out cardiac arrest survivors from other patients with thickened heart muscles (hypertrophic cardiomyopathy) who have never had serious rhythm abnormalities. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbbdJugJLCLZfQYimqdLU2ypjWBvFUJgwau1CRdOHJ2P-2FEAAaVX2rTGOu1B0mk3bHwIkFA1p3CU1haOqYyHruwH0-3DaEeo_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI4sgJeu3h-2BtoWiMWUtidIFm99aJFb-2FBOrYE6xqrrftmvvJZAcriv4h4xecaffPcdmUuzUO8-2BxpzoVo93ndUXKid-2Fiin7nn-2Bm85j-2BH2PmhJuF9xioZhdNkbUW9r2wWDxq0upAY2cxFwyKxo1t9NakPtE-2FykJkmdEnVZNeL4Xi1D6Q-3D-3D&data=05%7C01%7Cfulham.rec%40hra.nhs.uk%7C792e816d951f4b29fc3308dbac481d4f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638293197949406377%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=oFSKyKWdxD9TbpVRKLZvIOe%2BFynnYoMrKTPLP24D39Q%3D&reserved=0 page S31.
We now have a better understanding of the electrical problem that leads to cardiac arrest and the tools we might be able to use to pre-empt it. This study has revealed several new ideas that can be tested in clinical trials to see whether they make a difference in a wider population.All the research done in these studies was looking back at patients with previously known cardiac arrest to see if this could be measured electrically compared with unaffected volunteers – known as ‘retrospective’ measurement. To understand whether these measurements will work as a mainstream clinical tool, researchers must study the numbers in a group of people who have not had a cardiac arrest yet but might do in the future – this is called ‘prospective’ testing.
We have set up another study called PREDICT-VF2 – which will look at 200 patients with hypertrophic cardiomyopathy who have never had a cardiac arrest. We will manage them according to modern guidelines to ensure they receive the best known treatments, but also make electrical measurements at the start of their 5 year follow-up to see if these would have been better predictors than the current guideline-backed tools.
So far we have recruited 67 out of the target 200 volunteers and expect to release our final results in 2027.
REC name
London - Fulham Research Ethics Committee
REC reference
17/LO/1660
Date of REC Opinion
22 Nov 2017
REC opinion
Further Information Favourable Opinion