Dr Michael Papadakis answers some of your questions about their recent research publication identifying the importance of routine ajmaline testing after a SADS death.
Q. When families are referred after a sads death to the CRY Centre for Inherited Cardiac Conditions at St George’s Hospital would they always/usually have the ajmaline test on the same day as all the other tests?
A. Yes we do Ajmalines same day for the great majority. We may not if:
- The PM casts doubt regarding diagnosis i.e. there is some structural issue but no diagnosis such as idiopathic fibrosis or idiopathic LVH when I prefer to do an MRI first prior to Ajmaline.
- The investigations in any relative is suggestive of a potential structural cause.
- Middle-aged relative with arrhythmia try to exclude coronary disease or cardiomyopathy before Ajmaline.
- Family member not keen.
Q. My child died from SADS. Both of us (the parents) and our child were referred for further testing. Should all family members have had an ajamline test?
A. We used to Ajmaline everyone in the past and we definitely offered it to most people in the paper published in March 2018. As a result of our and others research our practice has changed. It is possible to have a polygenic disorder, which Brugada probably is, that the combination of parental genes may cause the disease in the child and we have definitely seen positive Ajmalines like that in our cohort but in a tiny number of cases, which to be honest you are not sure how to interpret them.
So given the challenges of Ajmaline testing we have taken a more pragmatic approach and we won’t offer it to children when the results of both parents are completely normal (including the ajmaline tests) and the baseline investigations of the children (ECG, ECHO, exercise test…) are completely normal. We could still offer an Ajmaline to a child of negative parents (on a case-by-case basis) if for example:
- The children have a suspicious looking ECG at baseline.
- The Ajmaline of dad or mum look suspicious but not diagnostic.
- A child may be Ajmalined irrespective of the parent result is if they happen to be referred earlier i.e. the daughter is referred first and then we see (or not sure if we will ever see) the parents or the daughter comes with one of the parents only.
Q. My child died of SADS 15 years ago. At the time we were not offered ajmaline tests, we just had an ECG and an ECHO. Should we have had these tests, what should we do now?
A. At the CRY centre we have been routinely doing an ajmaline test after a SADS death for just over 10 years. This was not always routine practice and it has not been routine practice within some Inherited Cardiac Conditions Centres throughout the UK. We would recommend you contact the ICC centre in your region and ask them to review your original tests and to ask for them to conduct comprehensive testing on first degree blood relatives of the child who died. It is possible that 15 years ago when there was less understanding of SADS that the cause of death could have been structural (e.g. a cardiomyopathy). The post mortem should be reviewed and if there is any concern the cause of death was a structural problem then an MRI may be warranted.
Q. Is SADS the same as young sudden cardiac death? If someone dies young from cardiomyopathy is this called SADS?
A. If a young person dies from cardiomyopathy this is considered a young sudden cardiac death (YSCD). However, it is not considered a SADS death. A SADS death is when the cause of death is unascertained but all possible causes of death are excluded leaving the probable cause of death to be cardiac. SADS deaths are usually caused by conditions like Long qt, Brugada, CPVT, WPW. SADS is due to an electrical problem and after the death there is no evidence of structural changes to the heart.
Q. My child died of hypertrophic cardiomyopathy. Should family members have been offered an ajmaline test?
A. No. If the cause of death was established as a structural problem then the further tests of family members should focus on that specific condition. This may include an ECG, ECHO, Exercise test, holter monitor and in the case of Cardiomyopathy an MRI. Genetic cascade testing may also be offered.
Q. If the individuals who are at risk for having brugada, when they have the ajmaline infusion, what response does that infusion mimic in terms of an in-life response? Does it represent a phase when resting, does it represent a phase when scared or alerted?
A. What ajmaline does is blocks some of the Sodium ion channels. These are the same channels that are defective in Brugada syndrome. In most individuals Ajmaline will cause some ECG changes but nowhere near enough to mimic the diagnostic Brugada ECG pattern as they have “normal” sodium channels and they are able to cope/compensate. In those with Brugada syndrome the ion channels are defective and by adding a sodium channel blocker you provoke the ECG pattern, as they do not have the normal reserves. So in a way ajmaline makes the situation temporarily worse (makes the electricity of the heart more unstable) to allow us to diagnose the condition. As it is a very short acting drug it is out of the system within minutes. Ajmaline is not a stress test i.e. does not mimic exercise or anxiety.
Q. How do you not know that for every 10 or 20 healthy individuals, that an ajmaline test just happens to cause a benign ecg pattern that’s only seen when given this chemical? Are there any studies suggesting a clear response to a selected portion in terms of brugada and ajmaline?
A. This is an excellent point and it is possible that some of our positive results represent what we would call a false-positive i.e. the test is positive but the individual does not have the condition. We know that no test in medicine is 100% accurate. There are always a few false positives or even false negatives even with accurate tests. In the past few years, concerns have been raised about the specificity of ajmaline test which have been predominantly based on a Turkish study i.e. having a high false positive rate in other words a positive test not indicating disease. Our estimate is that the ajmaline test may be falsely positive in 1 in 20 individuals we test i.e. 5% and we think this is the worst case scenario. However, it is important to remember that is is different to do the test in an otherwise “healthy” population and difficult to ignore in a family who just lost someone. In addition you can look at other clues such as multiple family members in the same family being the most important. This point is discussed extensively in our paper.
Q. Once the individual has gone through a negative result from ajmaline, does this necessarily mean they are brugada free?
A. This is an excellent point and it is possible that some of our negative results represent what we would call a false-negatives i.e. the test is negative but the individual has the condition. We know that no test in medicine is 100% accurate. There are always a few false negatives or even false positives even with very accurate tests. It is important to emphasise that we always advise families that should they experience any new symptoms they should come back to us and not be reassured by their negative screening. However, it is important to emphasise, that we are also extremely reassuring to individuals with a completely negative screening, particularly if multiple family relatives. Even if one assumes that an ajmaline test is falsely positive the risk of that individual would be extremely small.
Read the research paper on the Journal of the American College of Cardiology website.
