Is There a Link Between Gasoline Vapors and Brugada Syndrome?Interview with Darko Kranjcec, MD and Hugues Abriel, MD, PhD

Tell us about this case report. A 46-year-old male presented to the ER after experiencing two short syncopal attacks while working the night shift at a gas station. The patient had had accidental exposure to important amounts of gasoline vapors; he mentioned that he never had had such exposure previously. Still at work, he felt dizzy and nauseous. Thus far, the patient had been in good health. He occasionally had dizzy spells that were not related to his work. However, this was his first syncopal episode. In the past, he had routine medical examinations by his GP; unfortunately, no ECG was performed at that time. The patient s history did include a cousin who died suddenly at a young age from unknown causes. No autopsy was performed on this relative, but before his death he was in good health and had no complaints. In the ambulance while en route to the hospital, the patient was defibrillated from ventricular fibrillation (VF). Upon arrival to the ER, his ECG showed a typical type-1 Brugada pattern. Since all known causes of pseudo-Brugada syndrome were excluded and analysis of the gene SCN5A showed a pathogenic mutation, an implantable cardioverter-defibrillator (ICD) was implanted. Did this patient have a family history of Brugada syndrome? In this case, we cannot yet say that there is a family history of Brugada syndrome since we did not perform genetic analyses on the patient s parents. Moreover, the two sons of the patient were shown not to carry the SCN5A mutation. Sporadic cases of Brugada syndrome are quite frequent. The significance of the sudden death of the patient s cousin is unknown. Does Brugada syndrome often appear later in life? Most of the time Brugada syndrome is diagnosed in males in their 30-40s, but the range of ages is very broad, from infants to patients in their 70 s. This was the first case report to make a connection between the BrS gene and the inhalation of gasoline vapors. How were you able to conclude that the cause of this patient s sudden cardiac arrest episode was due to the gasoline vapors? In the discussion of our case report, we indeed mentioned that this was the first case linking gasoline vapor exposure to a patient showing Brugada syndrome. However, the issue of causality is not a simple one. As discussed in our paper, it can be suggested that inhalation of gasoline vapors, in addition to many other clinical conditions so far described, may also be a triggering factor for unmasking the Brugada syndrome.¹ Therefore, after excluding all so far described factors that can ‘unmask Brugada syndrome, we concluded in this particular patient (since there was an obvious time correlation) that it may be the triggering factor. Why was this phenomenon not described earlier? Well, there is always a first time! Moreover, since Brugada syndrome was described as a clinical entity only about 15 years ago, there is probably a lot to discover regarding basic and clinical aspects of this disease. Future investigations will tell us if this was just an isolated case or if this presentation is more common, which may suggest a causal link between the exposure to these gasoline vapors and Brugada syndrome. Were you surprised by these findings? We were mainly intrigued by these findings; our goal of this case report was to share our observation with the medical, and in particular, the EP community. There have been some reports in literature about the health effects of gasoline vapor inhalation and/or glue sniffing; what do these studies show? Yes, there are described cases of sudden death after gasoline vapor or glue inhalation. However, none of these studies have linked it to Brugada syndrome. It may be speculated that some of the chemicals found in gasoline vapors may alter the function of cardiac ion channels, and that certain patients who have specific genetic variants (as seen in our patient) may be more sensitive to it than others. Prospective studies looking at mutations in the gene SCN5A in patients who either died or had arrhythmias after exposure to such vapors or glue may provide an answer to this interesting question. How is your patient doing today? The patient is doing well. He has not received any ICD shocks so far. However, he had several episodes of supraventricular paroxysmal tachycardia, which were successfully treated with beta-blockers. This patient s job was working in a gas station; therefore, will he have to quit or change his profession? Yes, the patient has now retired, since his employer had no alternative work for him. So he has never been exposed again to gasoline vapors, which might be the reason why he has not had any VT or VF episodes since. It was noted in your article that it was beyond the scope of this study to investigate which chemical may have been involved in triggering the arrhythmic event.¹ Will further research be conducted? In our study, we were not able to analyze which chemical may have been involved in triggering the arrhythmic episode. Before initiating a study aiming at finding out which of the chemical(s) found in these gasoline vapors may alter the function of cardiac ion channels, we are awaiting other similar reports that may reinforce a direct link between Brugada syndrome and these vapors. Should Brugada patients be tested for this gene mutation, or have special considerations when in contact with gasoline vapors? In about 20% of Brugada syndrome cases, mutations in the gene SCN5A are found. Most of these mutations are unique; there is an excellent publicly available database supported by the European Heart Rhythm Association summarizing the 100 mutations found in Brugada syndrome patients: www.fsm.it/cardmoc/. Recently, mutations in calcium channel subunit genes and an enzyme called glycerol-3-phosphate dehydrogenase 1-like gene have been reported. However, it looks like the mutations in these genes underlie only a few percent of all Brugada cases. Genetic analysis of the SCN5A gene should be encouraged in all Brugada syndrome patients, because it may permit a precise molecular diagnosis that could be important in borderline cases, and importantly, may demonstrate or exclude a disease-causing mutation in asymptomatic (or paucysymptomatic) family members. Ideally this process should be performed in the frame of genetic counseling for the whole family. At this stage, we do not think there is a specific genetic background that may explain the sensitivity to gasoline vapors. Do you believe patients with other arrhythmia conditions besides Brugada are also at risk? Yes. Based on reports of sudden deaths in persons voluntarily inhaling volatile substances of abuse (glue-sniffing), it can be speculated that patients with altered function of cardiac ion channels, such as congenital long QT patients or heart failure patients, may also be at risk of developing arrhythmias when exposed to these volatile agents. However, this point remains to be demonstrated in the future. Is there anything else you d like to add? The field of cardiac channelopathies is illustrating very well how progresses in molecular genetics and biology during the past decade has helped clinicians to better understand the etiology of thus far idiopathic disorders. Every day we are gaining more and more detailed knowledge about the mechanisms underlying rare but also frequent human diseases. It is very likely that these findings will provide us with new preventive and therapeutic strategies for patients with complex diseases such as cardiac arrhythmias.