false
Catalog
From the ECG to the Diagnosis: How to Squeeze Out ...
ECG Risk Stratification in Brugada Syndrome (Prese ...
ECG Risk Stratification in Brugada Syndrome (Presenter: Pier D. Lambiase, MBChB, FHRS)
Back to course
[Please upgrade your browser to play this video content]
Video Transcription
Before Dr. Nambiazi talks, I just want to point out the topic of this session has been emphasized with three speakers to really point out the importance of the EKG and its utilization prior to doing any invasive procedures. All right, thank you very much. So I'd like to thank the organizers of the meeting for giving me such a straightforward topic because this is quite a controversial area. The risk stratification of Brugada in itself and then the utilization of the ECG. Most important thing I want to say at the beginning is to be specific about the type one Brugada pattern because there is often an over-diagnosis of Brugada syndrome in ECG. Often because patients may have an incomplete right bundle pattern or a degree of ST elevation with an R prime in V1 or V2. That's not a Brugada pattern. It has to be coved with the absence of an R prime in V1. And this type two saddleback pattern, which is seen, may transition with an adjuvaline challenge test to type one, but in itself is not a Brugada pattern ECG. And indeed, there is an overlap. There are phenocopies. So if you see a patient with pectus excavatum with an RSR pattern and degree of ST elevation, that's normal for pectus excavatum. You don't need to subject the patient to an adjuvaline challenge test unless there's a family history of sudden death or unexplained syncope, for example. And similarly, patients with ARVC may have an epsilon wave in about 12% to 15% of patients and they can occasionally overlap with a Brugada pattern ECG. If you see an RSR in V1 and the QRS is wider in V1 than V6, think about there could be an underlying Brugada phenotype in these patients. Now there are two mechanisms which are proposed to the ST elevation on the ECG for Brugada. One is the repolarization hypothesis where there's notching of the essentially the epicardial action potential causing a conduction, a gradient, a voltage gradient from the endocardium to the epicardium given the ST elevation. Recent studies using ECG imaging specifically in patients as opposed to the wedge preparation where the repolarization hypothesis was derived have demonstrated that there are conduction delays within the right ventricular outflow tract which can account for these ECG abnormalities. We've also shown this endocardially and specifically there's probably an interaction between conduction delay enabling dispersion of repolarization and enabling these gradients to exist. Now the purpose of this talk is to discuss ECG risk stratification and this really comes from the statement of Hippocrates which is the job of physicians to declare the past, diagnose the present, and foretell the future. So can we use the surface ECG to foretell the future, predict risk in Brugada? The issue with Brugada is that there are dynamic changes in the ECG. Changes in vagal tone will promote dynamic changes in ST elevation and this series, this small series where families are identified with Brugada where there'd been a sudden death, when the ECG was obtained from the deceased individual, only about a third of those patients actually had a type 1 Brugada ECG in life. So it highlights how dynamic the ECG is and indeed when one looks at the finger registry which has a thousand patients and they attempted to look at risk factors for sudden cardiac death or VF arrest, only unexplained syncope and a prior cardiac arrest was a risk marker. They didn't actually look at the ECG but it suggests that it's extremely challenging the fact that they didn't do that and indeed there's, as most of you will be aware, there's a lot of debate about utilizing VT stimulation studies to predict risk and at the moment the jury is still out as whether any form of VT stim is useful and this, I think the main challenge for this comes from the fact that the risk of spontaneous VF in Brugada is 0.3 to 1% per annum, so you're trying to discern a very low risk from a relatively non-specific test. When one actually reviews the literature in terms of the ECG markers, the main markers that stand out are essentially a spontaneous type 1 ECG, QRS fragmentation, early repolarization and two other markers, an S-wave pattern and the AVR sign. So I'm going to go through each of these markers in terms of how they display on the ECG and what their predictive power is. Now fragmented QRS can be identified but you need a wideband filter on the ECG between 0 and 150 hertz, a bit like looking for late potentials. One may see fractionated signals in the ST segment. If you use a narrowband filter, 0 to 25% hertz, you may miss it. This comes originally from a study by Morita where 58% of the patients with fragmented QRS actually had a history of ventricular fibrillation compared to those which only 6% which were negative. Another paper from the PRELUDE study from Silva Priori, they looked also at QRS fragmentation but they had a different definition, more than two components of the QRS and T-wave predicting risk. But this didn't come out on motivariate analysis, only on univariate analysis as a risk marker. This lists all the studies that have used QRS fragmentation and most of them are associated with a history of VF but not necessarily predicting future VF events. An important marker is the early repolarization pattern which has been identified in a number of studies being associated with an increased risk of VF and Brugada syndrome. Now there's been a recent consensus statement which has specifically defined early repolarization that there is either notching in the QRS segment, in the ST segment, but there has to be at least 0.1 millivolts of ST elevation in two or more contiguous leads. The QRS has to be less than 120 milliseconds. And if you see slurring, one needs to see an angle of more than 10 degrees between the lower component which is slurred and the downslope of the S-wave for it to be defined as a slur. These are very specific criteria, but we need these if we're going to go forward in terms of utilizing any of these ECG risk markers for risk stratification. Looking at the data, 12 to 15% of patients with Brugada have early repolarization and if there's a flat ST segment with early repol, this has an 11-fold greater risk of VF arrest in these patients. Overall, on meta-analysis, the hazard ratio of having early repol, of being associated with VF, is threefold. So it's quite a strong risk marker. Indeed, if you have persistent early repolarization, indicating almost certainly a greater dispersion of repolarization of the epicardium, there's a fourfold increased risk of spontaneous VF and STORM. And indeed, taking this concept further forward, one may actually see a Brugada pattern in the peripheral leads, such as an AVR, or the peripheral leads on the chest leads. This again is a marker of increased repolarization abnormality on the epicardial surface. And in this large study of 234 asymptomatic patients initially, if you had this pattern, the pre-cordial plus sign, with a Brugada type 1 ECG, 13% of these patients went on to have a VF arrest, compared to those with only 3% with a classic Brugada pattern, without peripheral early repolarization in terms of the type 1 Brugada pattern in the peripheral leads. Another marker that's been reported recently in Jack was this S-wave from Kalo, a Spanish group, and looked at over 200 patients. He identified that if you have an S-wave of more than 0.1 millivolts or 40 milliseconds in duration, this was associated with a 39-fold greater risk of VF. So one might think this is a very strong risk marker, but essentially, when one looks at the negative and positive predictive value, very high negative predictive accuracy, but low positive predictive accuracy. So a helpful marker if it's not present, but not particularly helpful if it is. The mechanism almost certainly is due to conduction delay in the right ventricular outflow tract, as they demonstrated with endocardial mapping, slow conduction away from the left side of the septum, promoting this S-wave pattern in lead 1, compared to normal controls. Final resting ECG sign is this AVR sign, which again, is a prominent R-wave in lead AVR, promoting later depolarization in AVR, and a specific amplitude and R-Q ratio criteria are given. This has only been reported once in 24 patients as a risk marker, so I've just put it there for completeness, but I don't think it's a particularly strong risk marker. What's really of value is the fact that since BRUGADA, you get dynamic changes related to changes in autonomic tone, is if one can demonstrate that there are dynamic changes on the ECG in this particular Japanese study, looked at the augmentation of the type 1 pattern in recovery on exercise. So during recovery of exercise, there's sympathetic withdrawal and promoted vagal tone, and this can therefore bring out the BRUGADA type 1 pattern in ECG. The mechanism of this, again, relates to the repolarization hypothesis, because as the increased cholinergic tone, the KCH channel is activated, which will shorten the epicardial action potential and potentially promote this gradient. We were interested in this mechanism, so we took a group of our BRUGADA patients and recorded endocardially and epicardially, and recorded the activation recovery interval, which is a surrogate of action potential duration, on a unipolar electrogram. And you'll see here in the dotted line on the epicardium, I'm not sure the arrow is working, but yes, the epicardium, you have a shorter action potential duration on the epicardium versus the endocardium compared to normal patients without BRUGADA where it's the other way around. And when one gives edrophonium, which inhibits the uptake of acetylcholine in the synaptic cleft, or sorry, breakdown of acetylcholine in the synaptic cleft, you end up with a much larger gradient. So essentially, the increased cholinergic tone promotes an endo to epicardial gradient and therefore could enable the potential for phase 2 reentry to occur in BRUGADA. And indeed, when they looked at these risk markers, the Japanese group, they looked at gene status and also prior VFRS, the dynamic change in the ECG in recovery was an independent predictor, as was a prior history of VF. So the fact that one can take individual risk markers is interesting, but actually hasn't proved to be very helpful in trying to identify individual risk. And this has resulted in a drive to try and combine risk factors using the ECG or the clinical history to predict outcomes. And the first to do this was Deleese, and he looked at syncope, a family history of sudden cardiac death, and a positive EP study. And if you had two or more of these risk factors, you had a significant event rate, up to 25% over five years. Indeed, looking at single ECG risk markers, Japanese group looked at 246 patients, and they showed if you had early repolarization on the ECG and or a fragmented QRS, again, you predicted a significant event rate. The BRUGADA group looked at their own patients. They had 400 patients in this study, of which about 20% had a resting type 1 ECG. They had a derivation and validation cohort of 200 each, and they showed four specific risk markers, symptoms of unexplained syncope, sinus node disease, inducible VTVF at EP study, and early familial sudden cardiac death were independent predictors. They integrated this into a risk model. So you can see here, for example, if you have an early family history of sudden cardiac death and a spontaneous type 1 ECG would score two points, which would give you about a 10% risk over five years of having a cardiac arrest. So giving some measure of risk. This was a single population that they studied of their own patients. And the field is muddied by the waters of different groups having patients of different degrees of risk, and trying to apply these risk markers across the whole population is a real challenge. So we sought to address this question by working with a number of our collaborators in Europe and Brazil. This data was presented yesterday in the poster session in the evening. We looked at a cohort of 1,084 patients. But specifically, we weren't interested if you'd had a prior cardiac arrest, because that's a well-established risk marker. We wanted to look at patients who hadn't had a prior cardiac arrest, but had a spontaneous or induced type 1. And we then looked at their ECGs independently and looked at all the ECG risk markers that I've gone through and described to you, plus one or two others. And then we looked at their family history. And essentially, we've identified five risk markers from this cohort. This is an example demonstrating a peripheral type 1 pattern in this particular patient in that population. And essentially, we identified early repolarization, a spontaneous type 1 ECG, a family history of sudden cardiac death under the age of 40, which is unexplained, or arrhythmia-related syncope, as well as a Brugada type 1 pattern in the peripheral leads. And indeed, by looking at the hazard ratios and working with a clever epidemiologist, one can actually then integrate this into a risk score by ascribing specific points to each of these individual risk factors. So that, for example, if you had a type 1 Brugada pattern in your peripheral leads with early repolarization in the peripheral leads, that will give you a score of 20. And then essentially, you can read off the risk in this group. And that patient would be about 8% over five years, which would be a threshold at which you would strongly consider an ICD. For example, if you look at the Hoken risk score, we would say a 6% threshold at five years would be a risk mark, would be a threshold to implant an ICD. Indeed, we validated this within that cohort with bootstrapping, looking at observed and accepted events. And the area under the curve for this risk model is 0.83. The Sierra model from the Brugada group, which I showed you, has an area under the curve of 0.7. So if one summarizes the risk markers, and essentially the consistent risk markers of an ECG that seem to be prevalent to predict actual events in Brugada as opposed to a prior VF arrest are certainly a peripheral type 1 pattern in ECG, early repolarization, and in some cohorts, QRS fragmentation. But it's clear that we need to think about using multiple ECG risk markers, looking at conduction repolarization to potentially predict risk in Brugada. The most consistent seem to be associated more with persistent abnormalities in repolarization in the standard and the peripheral leads. But the changes are transient, so dynamic testing to bring out, for example, vagatonic maneuvers to bring out the Brugada pattern could be of value. And integrating this almost with genetic risk scores could be of value overall in identifying the highest risk groups. I'd just like to thank my collaborators for the risk score that we're developing that helped with this, with the growth-strength manuscripts and preparation. Thank you for your attention.
Video Summary
Dr. Nambiazi discusses the use of electrocardiogram (ECG) for risk stratification in Brugada syndrome. He emphasizes the importance of correctly identifying the type 1 Brugada pattern and differentiating it from other ECG abnormalities. He explains that there are two proposed mechanisms for the ST elevation in Brugada syndrome: repolarization abnormalities and conduction delays in the right ventricular outflow tract. Dr. Nambiazi discusses various ECG markers that have been associated with increased risk of ventricular fibrillation (VF) in Brugada syndrome, including fragmented QRS, early repolarization pattern, S-wave pattern, and AVR sign. He explains the significance of dynamic changes in the ECG and the challenges in predicting risk based on individual risk markers. He also presents a risk score model that combines multiple ECG markers and family history to predict the risk of cardiac arrest in Brugada syndrome. This model shows promise in accurately identifying high-risk patients who may benefit from implantable cardioverter-defibrillator (ICD) therapy.
Meta Tag
Lecture ID
4043
Location
Room 201
Presenter
Pier D. Lambiase, MBChB, FHRS
Role
Invited Speaker
Session Date and Time
May 09, 2019 10:30 AM - 12:00 PM
Session Number
S-010
Keywords
ECG
Brugada syndrome
risk stratification
ventricular fibrillation
ICD therapy
Heart Rhythm Society
1325 G Street NW, Suite 500
Washington, DC 20005
P: 202-464-3400 F: 202-464-3401
E: questions@heartrhythm365.org
© Heart Rhythm Society
Privacy Policy
|
Cookie Declaration
|
Linking Policy
|
Patient Education Disclaimer
|
State Nonprofit Disclosures
|
FAQ
×
Please select your language
1
English