Brugada Syndrome (BrS) is a heart condition discovered in 19921 that is estimated to affect 5 in 10,000 people2, causing irregular heartbeats in the ventricles2 which results in ventricular fibrillation (VF)2. This causes purposeless tremors2 in the ventricles, therefore sudden cardiac arrest2. BrS is diagnosed by a right precordial ST-segment elevation followed by a negative T-wave on leads V1-V3 of an electrocardiogram (ECG)1. The condition is known to be the most prominent cause for sudden cardiac death in young people, especially men in southeast Asia, who otherwise have structurally normal hearts1. The most common mutation found in BrS patients has been in the SCN5A gene1 which codes for the alpha subunit of the cardiac sodium channel4. This leads to reduced flow of sodium ions into the cardiac myocytes, disrupting the heart beats and leading to arrhythmia3.
Presently, the main treatment for the management of BrS for symptomatic patients is the implantable cardioverter-defibrillator1 (ICD) however this is quite expensive and is known to cause many complications1 shown in table 14 including inappropriate shocks5 and electrical storm5.
Type of complication How it affects the patient
Access-related Caused while gaining access to section of the heart – includes haematoma, pneumothorax and haemothorax
Lead-related Caused by placement of the lead – includes fracture, need for lead emendation, dissection for use of tamponade
Generator-related Generator can fail due to erosion or migration which would need to be corrected
Infection Antibiotic therapy would be needed, or device would need to be extracted
Therefore, it is important to consider other methods of managing BrS that could potentially be future therapies for the patients suffering through this condition. One drug called isoproterenol (ISP) was given in low doses to seven patients who all had continuous syncope episodes and had been resuscitated from ventricular fibrillation (VF) or cardiac arrest6. An initial dose of ISP, 1-2μg6, followed by 0.15-0.30μg/min6 was given intravenously as an injection to the seven patients6. When the ISP was stopped the next day, ventricular arrhythmia (VA) reappeared in three patients before it was given again and after the fourth day, VA did not recur again in two of these patients6. The ST-elevation decreased in the ECG recordings and the difference between the ST-levels before and after the administration of ISP6 was recorded and calculated using the Wilcoxon’ signed-rank test which gave a probability value of less than 0.05, indicating that the difference was significant6, and this was shown by the VA disappearing6. However, in the remaining one patient, VF occurred again on the fourth day when ISP was stopped but when 400mg6 of oral quinidine sulphate was added to another ISP injection6 the VF stabilised6 and they did not suffer any more symptoms6. The low, continuous dose of ISP is significant because this study inferred that it was the reason for the participants not going through any side effects6. Limitations of this study included the ECG recordings being taken only once a day6 and since ECG parameters can vary throughout the day6, there could be a possibility that the ECG changes were due to this6. Also, this study is observational6 in terms of looking at the ECG pattern and interpreting it therefore it is challenging to be certain whether the results were because the arrhythmia responded to ISP or if it was stabilised spontaneously6. The sample size may also be considered to be too small to be representative of the entire population affected with BrS but since the use of ISP was proved to be effective in seven patients, it may be just as successful in a cohort of more patients if a larger clinical trial is undergone.
Quinidine is another drug which is currently being tested for the prevention of sudden VF episodes in BrS7. One study evaluated 25 participants7, 24 men and 1 woman7, all of whom had inducible VF7. Quinidine was found to inhibit VF induction in 22 out of the 25 patients7. None of them had any arrhythmic events2 in the follow up check from 6 months to 22.2 years7 so although the sample size is small, this study proves that quinidine has shown to effectively prevent VF7 in varying types of BrS patients. This was proven by the fact that 15 of the participants were symptomatic and 10 were asymptomatic7. When quinidine stopped being administered, 9 patients suffered through side effects7 and there was no control group7 to compare the findings to therefore this affects the complete efficacy of the drug. Overall, quinidine could possibly be a safe alternative to ICDs7 however figure 1 shows the major limitation of it being inaccessible to the vast majority of countries being surveyed which could affect patients’ survival rates when suffering through constant ICD shocks8. This is due to multiple case studies found such as a 30-year-old man from Mexico who suffered through VF storm8 and received quinidine for more than 5 years without any VF episodes but after quinidine was discontinued in Mexico8, an appropriate ICD shock due to VF was delivered to this patient8. This patient did not suffer through any more arrhythmias for the 6 month follow up period8 but it took 8 days8 for the quinidine to arrive which could have been detrimental to his health as BrS is known to cause sudden cardiac death1.
Figure 1 adapted from reference 7 showing the results of a survey from 273 different physicians from 131 countries about the availability of quinidine in their country’s healthcare system.
Another potential treatment for BrS may be epicardial radio frequency catheter ablation for substrate elimination,9 where radio frequency energy is utilised to heat tissue around the right ventricular outflow tract10 and this helps block the abnormal electrical impulses11 which cause BrS. It is suggested that the electrophysiological mechanism causing BrS is the delayed depolarisation of the ventricular outflow tract epicardium therefore ablation of this area can regularise the type 1 BrS ECG pattern. One study presented a 52-year-old male who regularly showed a type 1 Brugada pattern on an ECG regularly9. Six months after ICD implantation, this patient received an appropriate shock due to VF9 and even after ten months of quinidine administration, this continued.9 So, he underwent the catheter ablation procedure. After a follow up period from three to fourteen months9, this patient did not experience any more syncope, VF episodes or any form of VA and stopped quinidine treatment for eleven months with the same results9. This shows that this method was effective in treating BrS in this patient, but this study only considered one patient, and this could be due to chance, so this conclusion cannot be made for all BrS patients without larger clinical trials.
After a ten-month follow-up12, another study concluded that the catheter ablation is effective in potentially abolishing the VA in 98.5% of 135 symptomatic patients12 who initially had ventricular tachycardia and VF symptoms12 therefore it is much more reliable as the sample size is larger. The 1.5% of patients whose ECG pattern did not normalise, did so after a second procedure which proved to be effective12, deducing a 100% success rate for this trial. Another study including nine people13 who suffered from a median of 4 VF episodes in the month prior to the study due to ICD discharges13 showed the regularisation of the ECG pattern (as shown in figure 2) after epicardial ablation immediately in 55.6% of the patients and within three months for 42.9% of the patients13. The remaining 1.5% showed regularisation 33 months after the ablation with the aid of amiodarone treatment13.
This study further emphasises how effective this ablation technique can be as everyone reacted to it at different times, but the end result was no VF recurrences. Also, the Brugada ECG pattern was not a spontaneous result but was consistent over many years13. However, this was a small sample size, all of whom desperately needed effective treatment for their VF episodes due to not responding to anti arrhythmic agents so perhaps the result may have been different for patients who were not using this technique as a last resort for treatment. The risks of ablation include damage to the heart’s regular electrical pathways11 (requires pacemaker to correct11) and haematomas11 however this risk is considered to be small and the benefits outweigh the risks of the procedure.
In conclusion, epicardial radiofrequency catheter ablation is likely to be the most effective treatment for Brugada syndrome in the future because it has proved to show the most improvement in preventing abnormal heart rhythms in the largest sample of patients. However, more research needs to be undertaken to determine whether ablation can replace the use of an ICD in a large sample size of high-risk BrS patients13 in order to form a firm argument that this treatment should be available universally. However, catheter ablation could be too costly for certain patients to afford therefore it is important that anti-arrhythmic drugs like quinidine are readily available in many more countries so that VF episodes can be managed effectively, and patients can have a better quality of life.