COMMENTARY

Brugada Syndrome vs Pattern: What You Should Know

Rajiv Gulati, MD, PhD; Suraj Kapa, MD

Disclosures

November 17, 2014

Editorial Collaboration

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Brugada: Multifaceted and Misunderstood

Rajiv Gulati, MD, PhD: I am Rajiv Gulati from the Division of Cardiovascular Diseases Mayo Clinic, Rochester, Minnesota. I am joined today by my colleague, Dr Suraj Kapa, who is also a cardiologist, and specializes in electrophysiology (EP).

We are going to talk about Brugada syndrome. What is Brugada syndrome?

Suraj Kapa, MD: It is commonly misunderstood. Brugada has been recognized for decades as a syndrome. It is an abnormality in the ion channels of the heart, resulting in abnormalities in how the heart cells activate. In turn, this can result in patients suddenly dying. They can be walking down the street and experience sudden syncope or sudden death, unless there is somebody around to resuscitate them. It is estimated that 0.1%-0.6% of the population carry the genetic characteristics that may put them at risk of being affected by Brugada syndrome.

It is important to distinguish between the Brugada pattern and the Brugada syndrome. Many patients have an ECG that shows Brugada pattern, but that does not necessarily mean that they have the syndrome or are at risk for sudden death, although all of them may have genetic abnormalities that cause the problems in the ion channels.

When we look at Brugada syndrome, we come to understand that it is a much more multifaceted disease than just a genetic mutation or an abnormal ECG. We put all of those factors together into the diagnosis.

Dr Gulati: As a non-EP guy, I worry about missing the Brugada pattern on the ECG, but I also worry about overdiagnosing. Could you elaborate on the challenges in making the diagnosis?

Dr Kapa: The truth is that Brugada can be extraordinarily challenging from both estimations. Other syndromes and diseases can look like a Brugada pattern on an ECG. The Brugada pattern shows abnormalities in V1 and V2 on the ECG in the two precordial leads. It is principally around the right ventricle and along the right ventricular outflow tract where we see the abnormality in terms of the substrate of the heart. That in turn creates abnormalities in those two precordial leads that are looking at the anterior surface of the heart.

Other types of diseases can show similar abnormalities. Arrhythmogenic right ventricular dysplasia can look very similar, and even a typical right bundle branch block can be mistaken for the Brugada pattern. You can see a baseline ECG that is suggestive of the abnormality, but it isn't Brugada syndrome.

The flip side is the problem of underdiagnosis. Not every ECG from the same person will necessarily reveal the Brugada pattern. Therefore, we need to be careful to review all ECGs, especially under conditions of stress, because sometimes specific stressors—fevers, use of tricyclic antidepressants, anesthesia exposure, and surgery—can reveal a Brugada pattern on ECG that was not present at baseline. It is important to consider patients who might come in with such nondescript symptoms as syncope, otherwise normal ECGs, or even seizures, which can be secondary to ventricular arrhythmias because of a lack of appropriate blood flow to the brain. Even with a normal ECG, provocative maneuvers might be necessary to bring it out.

Patient in Clinic: Possible Brugada

Dr Gulati: Let's say I see an ECG in a patient with a convincing story, and there is a concern for the Brugada pattern. Walk us through what to do next. How do we provoke or risk-stratify which patient needs invasive treatment?

Dr Kapa: If a patient walks into clinic after his or her physician was concerned about a possible Brugada pattern on an ECG, I talk to the patient to determine whether the patient has symptoms. Has the patient had episodes of suddenly passing out while walking down the street or doing something that would not otherwise be associated with feeling faint? Is the patient having seizures or other nondescript symptoms that might suggest an abnormal ventricular rhythm?

Once I establish that the patient has symptoms, and I look at the ECG and it suggests the Brugada pattern, much of my work is done at that point. We have found that patients who have symptoms and the Brugada pattern are at very high risk for further arrhythmic events. You can put 1 and 1 together to make 2, which would be the implantable cardioverter-defibrillator (ICD), without doing further strategies, such as EP studies or echocardiograms.

The difficulty is in patients who have an ECG pattern that suggests Brugada, but it's either not a classic pattern or the patient doesn't have symptoms. That is where the real problem arises. In the patient with symptoms in whom the Brugada pattern is suggested but not definite, we can take them to the EP laboratory and administer sodium-channel blockers (a flecainide or procainamide challenge) to try to elicit the Brugada pattern. Even before that, something that physicians commonly forget is that you can just move the V1 and V2 one interspace higher and elicit a classic Brugada pattern that goes along with having the syndrome.

In asymptomatic patients with no clear history of ventricular arrhythmia, we are in a bit of a pickle, because what do we do with those patients? We don't want them to have their first incident walking down the street and suddenly dying, and not having anyone around to resuscitate them. Over the past 20 years, people have looked into the world of EP studies to try to provoke the ventricular arrhythmias in the EP lab. One large group has suggested if you can provoke the arrhythmia during an EP study, then this is Brugada syndrome, and you put in an ICD.[1] Unfortunately, we have seen exactly the opposite in other large-scale studies, which say that it doesn't matter.[2,3]

Dr Gulati: You are talking asymptomatic patients here, correct?

Dr Kapa: Exactly. These are patients who have never had any symptoms or anything suggestive of a ventricular arrhythmia in the past.

Deciding on a Management Strategy

Dr Gulati: This is an area that is not resolved yet. At Mayo, do we have a belief in a particular strategy involving EP testing plus or minus ICD, vs a conservative watchful-waiting strategy? Do you have any personal thoughts on that matter?

Dr Kapa: Several factors go into it, one of which is genetic analysis. We recognize that there are certain genetic mutations. The most common genetic mutation is in the SCN5a-sodium channel that might be associated with a higher risk for an arrhythmic event in population studies.[4] Unfortunately, the lack of a positive genetic test does not necessarily mean that the patient doesn't have a genetic mutation, and that is the difficulty. The genetic mutation (and this is research that we have published on multiple different subjects) does not mean that a pathogenic mutation is causing the problem.[5,6] There is something called "background noise."

The next step is to talk to the patient about the potential risks. Some will say, "Look, this is the biggest fear in my life. I want everything done to reassure me as much as possible." And you might say, "Okay, let's do an EP study. If we don't provoke anything, all the data suggest that this is a very good negative prediction of having an arrhythmic event in the future." The problem is what to do with a positive EP study.

The other thing to discuss is how to monitor the patient. Maybe that weird symptom—that feeling of lightheadedness or palpitations—might have been a ventricular arrhythmia. An option available to us today is the implantable loop recorder. We can place a very tiny device underneath the skin that can record for up to 3 years, and we have preset criteria to identify ventricular arrhythmias.

Who Needs an ICD?

Dr Gulati: Identifying those at low risk seems like a nice option and can be reassuring, but trying to figure out who is at high risk remains a challenge. You mention that this is a local problem; it is confined to a region in the right side of heart. Why not just ablate that area?

Dr Kapa: This has only recently been understood. People have looked at the pathology of the heart in patients with Brugada syndrome. Why is the ECG localized in that area? The original pathology studies demonstrated that there are fatty changes within the epicardial surface of the anterior aspect of the right ventricular outflow tract. This prompted many people to ask, "If this is localized, why can't we take care of it by addressing the substrate?" Let's say somebody is having recurrent ICD shocks for ventricular arrhythmias or recurrent symptomatic ventricular tachycardia that doesn't necessarily result in shock. Why can't we do something about this?

At least a couple of investigators have demonstrated that by performing an ablation—where we burn the area of abnormal substrate, focusing on the epicardial surface—they not only prevent future ICD shocks, but the Brugada pattern also disappears on the ECG and is no longer provokable.[7,8] Of course, these studies are in small numbers of patients, and larger-scale studies are necessary to understand what we are seeing.

Dr Gulati: So, ablation hasn't yet replaced ICD, but it may be an adjunctive procedure for a certain subset of patients.

Dr Kapa: For these patients, the ablation may work. But if the ablation doesn't work, the patient is still at risk for a ventricular arrhythmia that can cause sudden death. In the high-risk patients who are judged to have sufficient risk to merit being concerned about the ventricular arrhythmia burden and the risk for sudden death, you still need to put in the ICD.

Dr Gulati: What else is on the horizon for Brugada?

Dr Kapa: One thing on the horizon is how to treat these patients with a defibrillator. We now have subcutaneous ICDs. One reason for all of this rigmarole about whether to put in an ICD is that putting in a transvenous ICD is not simple, and not without some risk. These are young patients. When we look at the epidemiology—if you go to south Asia, for instance—it is estimated that 50% of all unexplained sudden deaths in structurally normal hearts, in patients aged < 50 years, are a consequence of Brugada syndrome.[9,10] In European populations, it may be as high as 10%-30%.[11,12] You don't want to miss those.

The problem, however, is that these are young people. If you put an ICD through the venous system and into the heart itself, these leads can scar in place over time. If the patient has an infection 20 years down the road, it's not a trivial process to take these wires out.

Furthermore, there is a risk for inappropriate shocks in patients who can get their heart rates higher than 200 beats/min, because they are otherwise healthy. We don't want to put ICDs willy-nilly into patients who don't need them and will never use them. The subcutaneous ICD may change that to some extent, because it's not endovascular, so the risk for scarring in place isn't there inside the heart and removing it is simpler. The patient is still at risk for inappropriate shocks, and not everybody is a candidate for the subcutaneous ICD. Therefore, we still need to think about risk stratification and about better ways of understanding how to risk-stratify.

Among the factors we are looking at is how to better understand the substrate before putting in an ICD. If a patient's EP study is negative, and there is an abnormality in the right ventricular outflow tract on MRI, is the substrate enough to push us one way or the other? Are there other provocative maneuvers that might help us? Should all of these patients have a loop recorder? These are issues that we need to understand better, to more effectively follow these patients.

Dr Gulati: I have learned a lot from you, Suraj. I appreciate you sharing your knowledge. Thanks to everyone for joining us, and I hope it has helped you understand this fascinating condition.

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