Referrer events

Thank you. Several years ago at the European Society of Cardiology, I was one of four people that were designated as a legend a modern legend in cardiology, and the other was well known to many of you. John Kamm And he got up and he said, You know, the only thing about being designated a legend in your lifetime is the alternative. And so thank you. So it's a pleasure to be here. And I always love coming back to London so that you took on upstream therapy and atrial fibrillation. And the question is, does it work? Can we with various drugs and risk factor modification, prevent atrial fibrillation? Can we prevent progression from paroxysmal to persistent atrial fibrillation? Now, the essence of my talk is this and this is work that we've been involved with in Mayo Rochester for probably the last 20, 30 years. And that started off as the following the epidemic of atrial fibrillation, because it is an epidemic. There's no question the commonest arrhythmia, but the epidemic of atrial fibrillation, is it a vascular disease and the hypothesis was that risk factors like obesity, hypertension, age and atherosclerosis increase arterial stiffness. That in turn causes diastolic dysfunction, left ventricular hypertrophy that in turn increases the volume of the left atrium and a big left atrium has a larger degree. And big left atrium is electrically unstable and can lead to atrial fibrillation. And then somewhere out there is the role of inflammation left. I've left that as a question mark that keeps rearing its ugly head. We never quite have sorted out what the role is, but there probably is a role. And so this led to a whole series of studies, 2007 and then over the next ten years where we were able to show clearly that all of these risk factors were associated with atrial fibrillation, whether they cause atrial fibrillation, a little more uncertain, but they were associated and the clinical implications of the study were this, our first paper published in the Journal of the American College of Cardiology 2002 by Teresa Sang one of our colleagues. We showed that a dilated left atrial was a predictor of atrial fibrillation, an independent predictor irrespective of age and other things that just left atrial volume as a predictor of atrial fibrillation. But what really surprised us was a year later was this paper where we showed it is as much a predictor of stroke, MI, and cardiovascular death and coronary revascularization as it is of atrial fibrillation. And left atrial volume was almost like a barometer of the vasculature and the accompanying editorial from Dr. Pamela Douglas said LA. volume is the haemoglobin A1 c of diastolic dysfunction. And then I added to that and vascular disease. So I think left atrial volume is telling us quite a lot about the stiffness of the left ventricle and the size of the diastolic function in the ventricle and the stiffness of the arterial vasculature, which in turn is the result of atherosclerotic risk factors. So this is an abstract we're going to just has been sent to be presented at the American Heart Association meetings in November, 4900 patients, 27 not countries, counties in the Midwest. And these are patients with incident atrial fibrillation. And if you look at the number of chronic conditions in patients three years prior to the diagnosis of AF matched controls, 35% had no chronic condition, only in those with AF only 4% had no chronic condition. And by these chronic conditions already mean hypertension, diabetes, vascular disease and so on. And if you look at patients with three chronic conditions, 69% of those with AF matched controls 32%. So I really think that although atrial fibrillation is an arrhythmia and we treat it as an arrhythmia, we need to really think of it as a vascular disease. And that's important if we're going to try and prevent atrial fibrillation. And this was a paper written with Dr. George Weiss from Canada, who sadly recently died, but a very prominent electrophysiologist in North America. And we postulated here or that if you look at atrial fibrillation, it's not one disease at all. On one end of the spectrum, it's a disease that triggers triggers in the pulmonary vein. And these are patients that we used to call lone AF that means AF without any other disease. And although that term has fallen away, these tend to be young people. Maybe with a family history increased vagal tone. And then on the other end of the spectrum, you've got the majority of people that we all see with atrial fibrillation where age, obesity and atsclerotic risk factors are present and now you have a trigger, but you also have shown in grey a disease substrate atrial dilatation fibrosis leading to atrial fibrillation. And it's not just a disease of triggers, it's also a disease of a fixed substrate on the left and mainly paroxysmal on the right, mainly permanent. And somewhere in between is what's called persistent AF, and that is it's persistent, but you can call your victim out of it and then patients on the left very suitable for catheter ablation. But things have changed. Now as we were talking earlier, we now do catheter ablation earlier and earlier in the course of this disease. But these were most of the trials that have been published or in these patients in the seventies and eighties with atherosclerotic risk factors and a dilated left atrium. So let's look at the risk factors and their association with atrial fibrillation. This large national database from South Korea of a million subjects. And if you look at the adjusted rates for new onset atrial fibrillation and body mass index, pink is under the age of 60 blue over the age of 60. And there's a very strong association starting around about the age of the body mass index of about 25. And you can see an unequivocal association with atrial fibrillation. The other was smoking, particularly in pink in younger patients, very strong. And this is a very strong association with atrial fibrillation. And basically what this study showed was the emphasis on modifiable risk factors like weight and smoking and a greater impact in patients under the age of 60. And the guidelines in the US, the ACCAHA guidelines similar to the European guidelines said that it is weight loss. This is the 2019 update for overweight and obese patients with AF weight loss. Combined with risk factor modification is recommended and they made it across. One indication based upon B.R. is some randomised data and meta analyses and emphasised that there was no new data that demonstrate the beneficial effects of weight loss and risk factor modification and controlling AF. And I personally, when I send a patient for ablation, if they really are overweight, I like to try and see them lose weight over the next three months and may even use some of the ketogenic diets. But I've got a feeling that there is good evidence that if you can't get the weight down, that may reduce the risk of recurrences. There is a very strong association between obstructive sleep apnoea and atrial fibrillation. And if you think if you want to get an idea of the frequency of obstructive sleep apnoea, get on a plane in the Midwest, in the United States and you will see it's pretty frequent. These are papers that not all of them written by us, but the majority where we showed an association with the incidence of atrial fibrillation, the prevalence showed that of the direct current cardioversion patients with sleep apnoea are much more likely to relapse. Higher recurrence after RFA is radiofrequency ablation and the response to antiarrhythmic drugs was much is significantly poorer in patients with sleep apnoea. The mechanisms It's difficult to study sleep apnoea because when you study sleep apnoea, you've got a minimum. Most people with sleep apnoea have other comorbidities, so you're looking at obesity, metabolic syndrome, high inflammatory markers and it's very difficult to tease out patients with pure obstructive sleep apnoea and no other risk factors. But all of these factors can play a role in the development of atrial fibrillation. The other thing I think that happens if you think of sleep apnoea, it's a tremendously hyperactive autonomic milieu. These patients have both increased parasympathetic tone, increased vagal tone and sympathetic tone, and then when they obstruct, they get huge changes in the entire intra thoracic pressure, which results in increased wall stress, increased left atrial volume and atrial stress, atrial electrical and structural remodelling. And that leads to atrial fibrillation. And I think there is a very close relationship. Unfortunately, it's only really been one trial. And this trial, 579 patients with paroxysmal AF apnoea, hypoxia index of 15 or more. So they have moderate to severe obstructive sleep apnoea and they were randomised to usual care and CPAP and on the left it shouldn't be usual CPAP, it should be just usual care. And what did it show? Nothing. If you look at the CPAP group on the left at baseline and then three months, absolutely no change in the burden of atrial fibrillation. And if you look at the mean change in AF burden, this is the CPAP group in the last three months, usual care group, no difference. So rather disappointing. I've talked to my colleagues who really study sleep apnoea and they said pointed out it's a small trial. We don't actually know how well these patients adhere to therapy in a large number of people who put on CPAP just don't use it properly. So for what it's worth, there is a strong association with obstructive sleep apnoea, probably related in part due to obesity, but at least the one trial we have didn't show a benefit in terms of atrial fibrillation. That doesn't mean that we don't use CPAP. Obviously there are other benefits from sleep in patients with paroxysmal AF and obstructive sleep apnoea. Treatment with CPAP did not result in a statistically significant reduction in the burden of AF. But CPAP certainly plays a role in terms of quality of life. This is quite an interesting study that we did a few years ago. We looked at 15,000 patients who had exercise testing and where we had a measurement of the predicted functional aerobic capacity compared to what is predicted. And if you look at the these patients, the blue or those who had an excellent functional aerobic capacity of 104% or greater, the yellow with the least fit FAC less than 75%. And really what the study showed was that if you look at the freedom from atrial fibrillation over a 15 year period in people who are physically fit, there's a much lower rate of atrial fibrillation. Now, the many explanations for that, it may be that people who are physically fit or slimmer, they may smoke less than exercise more and so on. So it's confounded data. It's not direct proof, but it's pretty suggestive study considering it's 15,000 patients. So for whatever reason, physical fitness, which is good for you anyway, may reduce atrial fibrillation, but it's a j-shaped curve. And there are four studies that have shown in highly competitive aerobic athletes who have probably big left atrial because of the stroke volume they've got to generate particularly cross-country skiers. And there is an increase in atrial fibrillation. And later with age and these are just a number of studies. Marathon runners versus controls, hazard ratio for atrial fibrillation, 8.8 fold over time. And then one of the best studies, I think from Scandinavia, 52,000 long distance cross-country skiers participating in a 90 kilometre cross-country skiing event and the hazard ratio for AF in looking at the highest number of completed races. Vs those who only completed one race, 1.29 30% increase. And again those who had the fastest finishing times had a much higher late rate of atrial fibrillation many years later. And I think it's probably because of big left atrium and we seeing this in NFL football players. The problem with NFL players is when they stop playing, I mean, these are giants. And so when they stop playing and you've got a £300 man, you can almost be sure they have sleep apnoea. So it's but we are seeing more atrial fibrillation in the sports medicine clinic. What about blood pressure lowering? This is from one of the larger trials of Antihypertensives where patients were randomised to systolic blood pressure of less than 120 versus a pressure of less than 140 And the yellow was intensive, intensive treatment to get the blood pressure below. 120 This is 140 and if you look at incident cases of atrial fibrillation over a follow up of five years, significantly fewer in those with intensive blood pressure control hazard ratio of 0.74 P-value .037. And then in this analysis, it looks as though those patients with a blood pressure of less than 132 these are tertiles of blood pressure have the greatest reduction in subsequent atrial fibrillation. So it makes sense to control blood pressure. And we've actually looked at this in a different patient population in a registry at Duke University, and we've shown the same thing in a lot of talk about omega three fatty acids and vitamin D supplementation. This is a sub study of a trial called the vital trial. People over the age of 50 and embedded into their trial was another trial of with an endpoint being incident atrial fibrillation. Suffice it to say there was nothing there, no difference at all. P 0.19 for omega three fatty acids and vitamin D three which has had some kind of resurgence of interest in the era of COVID. Again, no effect, No effect on Atrial fibrillation. This is a this is a criticised trial for a number of reasons. The Prettyman trial, where people were randomised to a mediterranean diet enriched with nuts and extra virgin olive oil, 6700 for prevention patients, primary prevention. These were the Mediterranean diet and nuts group versus control in yellow. And if you look at extra virgin olive oil, there was a significant difference for what that's worth. But it's a trial that was criticised for a number of reasons in terms of crossovers and enrolment. And so what about caffeine? And this is, you know, when I was at nursery school in Zambia and primary school in South Africa, I was told that I learned that coffee causes atrial fibrillation, just part of we all knew that. So then along came a couple of epidemiological studies in the US, large studies that didn't show an association with caffeine consumption. In fact, the largest showed that people who drank more than three cups a day had less atrial fibrillation, which is a bit confusing. This is a really good trial and it's now published in the New England Journal. And about a month ago by a doctor, Greg Marcus, 100 patients smartphone mobile application and they were randomised to 14 days of caffeine consumption versus absence for 14 days and monitored during that time. So coffee consumption increased PVCs by 54%, reduced sleep by 36 minutes a night, increased Fitbit based steps, no effect on blood glucose and no effect on atrial arrhythmia. It is pretty impressive. Most of my and most of my cardiology friends love this study that just love it, and so do I think so. But it is a sting in the tail. If you look at patients who never had AF no history of AF that does not appear to be in association with caffeine consumption and atrial fibrillation. But in patients with a history of established AF caffeine is a has been shown to be a trigger 25 to 28% of the time. And I take care of a couple of colleagues at Mayo and if I called out and not one of them is urologist and he gets called out at night, he has a couple of cups of coffee and he's back in a food the next morning. So if you've never had a history, I would say moderate caffeine consumption is fine. But you will find patients who are adamant that caffeine will cause atrial phenomena. I'm not surprised by that. Alcohol UK Study UK Biobank 400,000 individuals. And whichever way you look at the data, it is clear that although there may be some reduction in atrial fib in people with mild alcohol consumption once it goes above 14 drinks a week is a very strong relationship. I don't know. You know the difference. Certainly it seems that beer and sin and spirits are more harmful than red wine and white wine. But be that as it may, I think there is a relationship between alcohol or at least moderate to severe alcohol consumption and atrial fibrillation. What about periodontitis and atrial fib the problem of looking at periodontal disease And any condition is that people with bad oral hygiene have many, many other risk factors. So it's difficult like sleep apnoea, to tease out pure effects of pure poor oral hygiene. And in the Appalachian states, in the stroke belt, in the states, West Virginia and some of those states where there is a very high incidence of cardiovascular disease, very high incidence of risk factors and really poor socioeconomic status, they talk about the ratio, the 2 to teeth ratio. So if you go to more tests and you have teeth, that's not a good thing. And it's probably, I do think that if you look at the data, there is a there's certainly a very plausible biological mechanism to explain why poor oral hygiene causing inflammation could result not just in atrial fibrillation but into other cardiovascular diseases, but difficult to study because this population is just a walking conglomeration of risk factors that this is an interesting study. I think it was from Japan, where they looked PISA, reflected the quantification of active inflammation of periodontal tissue, and then it correlated and doesn't look like such a strong correlation if you just look at that curve. But it is p .001 and it correlated with the degree of atrial fibrosis. Just really interesting study. And the clinical perspective is periodontitis can be a modifiable risk factor play if dental specialist should participate in comprehensive AF management. That was their recommendation. Well, this Danish prospective study also looked at chocolate intake and hey, you want anything to the left of the line is a reduction in atrial fibrillation. So what spoils this this relationship is really good. And if you. Keenan and you like eating chocolate this is a little bit worrying so what I would do is just simply just delete that from the paper. But accumulating evidence suggests that moderate chocolate intake may be inversely associated with AF risk. Well, there, like all of these studies, there's the potential for confounding. So to summarise and conclude, if we look at the modifiable risk factors, I think this curve, what this figure shows is the effect of the risk factor on AF and to the right, the effect of risk factor modification on AF. I think there really is good evidence for body mass index and AF and there is shown in green, there's pretty good evidence that if you can lose that this may have a favourable effect on recurrences of AF, although not everybody has been able to show that I might add. But very good study from Australia, although some people have not been able to repeat it, physical inactivity is a risk factor and as I showed before, I think that moderate reasonable levels of fitness reduce the incidence of atrial fibrillation, very high physical activity such as in competitive athletes may have a bimodal effect with maybe a reduction early on in AFib. But AFib in later life, sleep disordered breathing and obstructive sleep apnoea, I think there's no question that it's a risk factor, but whether we can modify it is open to question because at least the one trial was negative. Diabetes is a risk factor. Hypertension is a risk factor. And as I showed you, rigid control of blood pressure does appear to reduce the incidence of risk factors. Coronary disease. We just don't know. It's probably a risk factor, but we cannot say that modifying it would change the rate of atrial fibrillation, alcohol, clear data, cigarette smoking. We just don't have any data on smoking cessation. But there's no doubt that it increases. Yeah, atrial fib for whatever reason. And then I'm showing you the data with caffeine. But to close, irrespective of the strength of evidence linking specific risk factors to atrial fibrillation, what we treat when we treat these risk factors, we're not just trying to prevent atrial fibrillation, we're trying to prevent cardiovascular death and the overall benefits of controlling respect is indisputable. And quite frankly, I think this is a talk that often asks us to give. But the point is not to prevent atrial fibrillation. All of these risk factors should be modified because of common sense. And if you look at the Eric study, 13,000 patients, I don't know what the AHA is. The simple seven risk factors that contribute to cardiovascular health and and these are them stop smoking, eat better, lose weight, get active, manage blood pressure, reduce blood sugar, control cholesterol. And, you know, if you're able to do that, you get two points for each one of these three and six in. So if you were able to do that to a pretty large extent, look at the cumulative incidence of atrial fibrillation over 15, 20 years and inadequate would be in green where you have a score of you only actively reduce two of these risk factors and look at their incidence of atrial fibrillation. I mean, it is about 50% higher and the same applies to heart failure, same thing in independent predictors of incident, heart failure of the same respective and depending upon how many risk factors you had. So was this an effect on the relative risk of of heart failure? So the number of low risk lifestyle, lifestyle factors, a greater the less the risk of heart failure. And so the relationship really applies as well, I think, to atrial fibrillation and that is control risk factors for multiple reasons. So my final slide is in a we got a dog that behaves like this. We love love the dog dearly, but you can teach an old dog new tricks sometimes and it makes sense to control the risk factors. And I think they will reduce the incidence of atrial fibrillation, but they'll and they'll do other things that are beneficial as well. So I'll stop at that point.

So I'm going to try and take you through a very different talk around the screening for Risk of Sudden Death in the young. So I'm just going to try and put sudden death into into perspective for you. So we we have around 50,000 unexpected sudden deaths in the UK, some would estimate up to 100,000. But actually the recording of some Deaths are incredibly poor it's it's really inaccurate. The majority are due to coronary artery disease particularly in the older population and in the 1 to 35 year olds we think there may be up to 30, to 1500 unexpected sudden deaths per annum in that age group. And of those causes, one is cardiomyopathy, which is an inherited heart disease. Another is where the heart may appear normal after an autopsy is undertaken, which we've termed suddenly arrhythmic death syndrome, which is probably the the larger proportion of all. But there are many other causes in there, some of whom are of which are noncardiac. And I'll go through a little bit more detail later in the talk, but just to give you an idea of the sort of epidemiology we're thinking about in terms of the prevalence of disorders, hypertrophic cardiomyopathy, the most common cardiomyopathy one in 500 hundred and 20,000 people in the UK. Um, premature correlated disease, often due to familial hypercholesterolaemia another genetic heart disease 120,000. You've got Wolf Parkinson white syndrome, which is not genetic, but it's important. There is one of the potential risks long QT syndrome and not syndrome. I don't know how that got in there. Then one in 2000, that's still 30,000 Brugada syndrome, 30,000 Marfan syndrome, where we're looking at the most common cause of syndromic, a young thoracic aortic dissection. But there are other forms of aortic dissection also cause sudden death. And then one of the other cardiomyopathy say with mckenney cardiomyopathy still clocking in at several thousand in the UK population. So these are when you add those up, that's getting close to 300, 350,000 people with genetic heart diseases that may be placing them at high risk of sudden death and we have to identify them somehow. We can really I mean, short of screening everybody in the population. And we know that the screening committee in the UK is not interested in doing that because it's expensive. We can at least look at some high risk groups to start screening. And so of course, a symptomatic individual that may present primary care, particularly syncope and suspicious syncope. And I'll mention that at the end in particular, maybe a suspicious ECG finding somebody had their booth medical done and they've come up with some flagged findings that match the implicates risk or there may be family history. So a family history of premature sudden death or even unexplained sudden death, which is called sudden arrhythmic death syndrome. Um, where we've seen no evidence, as I said, of course, for the sudden death, even at an autopsy, or there may just be a family history of inherited heart disease, you may actually stumble across that when you interrogate the person more carefully. But I actually think in our population, people are less aware of the history of inherited heart diseases than the history of unexpected sudden deaths. And then there also athletes, which we'll touch upon as well, who are a bit higher risk for sudden death than the average. And those are the ones that tend to hit the headlines the most, as you would have seen with Christian Eriksen at the at the Euros a year or two back a few years back. There are some important considerations when we think about genetic heart diseases. Um, there's something called variable penetrance, meaning that the conditions are not always overtly present. So only in the proportion of individuals who carry them will they actually show signs of the disease, but they have susceptibility to it That may still be sufficient to cause sudden death in that individual or over time it'll develop. There's also other minor disease expression that may very difficult, may be very difficult to quantify, and often criteria that are generally accepted are not applicable when you're looking at a screening population. And the athletes heart in particular may have features that overlap with cardiomyopathy and sometimes even channelopathy, electrical heart diseases that make it difficult to diagnose. So I think looking at a cardiology referral to a specialist clinic rather than just a general cardiology list is important. If you want to get to the bottom of something accurately. And in fact, those are the international guidelines. Now referral to a specialist, a specialist service, the referral processes is complicated, but primary care is so critical and vital to the whole process. If there's been a sudden death, the coroner and the coroner's pathologist will be talking to primary care, and often it's primary care needs to guide the family after an unexpected premature death. Then it's primary care responsibility, often to pass the family on to cardiologists, paediatricians to geneticists. There may be sporting bodies doing screening, there may be schools doing screening as part of the cardiac risk In young screening program, for example, some of you may have come across and there may be the medicals that are just being done through executive care at Mayo or through BUPA medicals, etc., and those may come straight back to primary care for action or may be referred straight on, But primary care is going to be integral because you're going to pick up the pieces afterwards as well. So really, really important to to have that understanding of the processes and know who you're going to involve. So let's think about a family history of unexpected death. The first step is a coroner's post-mortem. If there's been an unexpected death, that's a standard process in our country. And thankfully that's in place because there to exclude unnatural deaths, deaths due to foul play. But the coroner doesn't need to necessarily tell you exactly what the cause is, as long as they've excluded the unnatural causes. But there's a tendency now and there's a progression education amongst coroners that the actual cause of death may still be relevant to the family. And we need to drill down further and further into that and involve doing proper coronial autopsies with reports doing histopathology, where the expert autopsy may appear to play a particular role. At my institution at St George's, we have the foremost quality pathologists in the country and one of the foremost in the world and it provide and it provides a critical role in be able to determine the cause of death accurately. We also need to know more about the victim's history, which includes liaising but liaison between the coroner and eventually the cardiologist to see the family on their reported history and their hospital records. But often these unheralded deaths, they're less likely to be a family history and less likely to be a heralding of symptoms or history in these genetic heart diseases. We need to try and identify them earlier, if possible. And then there's another potential role called the molecular autopsy, actually pioneered by one of my colleagues at the Mayo Clinic, Mike Ackerman, which is post-mortem genetic testing, where you will be able to identify the cause of death by doing genetic testing in material obtained at the autopsy. And we're slowly getting through to to coroners and pathologists about the importance of that at the time of autopsy, such that there's a there's a new NHS pathway that works closely with pathologists and coroners. And so now when we do look at autopsy series and this is actually one that comes from Ireland, but it's very similar across the world, similar results in Australia and New Zealand, Denmark, a lesson of the UK because our data reporting recorded that if you have a look at potential inherited and genetic causes in the 1 to 35 age group, you'll see at the bottom there, there's HCM, DCM, ARVC, LDH They're all meaning heart muscle, disease, types of heart as the heart muscle disease, most of which will be genetically mediated. There's also premature coronary artery disease you'll see as the second tallest peak. And this aortic dissection, aortic rupture. And as I said, you will see a genetically mediated. But the biggest peak is, is this group sad? Sudden Arrhythmic Death syndrome, which is the one that's most likely to be associated with electrical diseases. So if we detect an inheritable heart disease that's known to be in the family, then we should screen or we know that's in the family to screen as per that condition. So if we're going to identify cardiomyopathy, for example, so hypertrophic cardiomyopathy, we need to screen family members according to that. So an ECG and ECHO is a basic screening tool. Same with that as a cardiomyopathy and often cardiac and genetic testing may play a role in refining the diagnosis. And then we can go on to stratify the risk for the individual. But this is a standard screening process. So here we have an ECG of an individual with deep t wave inversion laterally on BCG and also in theory and then voltage criteria for left ventricular hypertrophy on these immediately highlighting electrical left ventricular hypertrophy. And then we can do a transthoracic echocardiogram. We can immediately point out evidence of septal hypertrophy support of a classical presentation of hypertrophic cardiomyopathy. Now there's another condition which is close to my heart, forgive the pun, but arrhythmogenic cardiomyopathy or right ventricular cardiomyopathy that's actually a lot harder to screen for. You can see there's quite a panoply of tests required to screen families for this disease and often cardiac MRI and genetic testing. underplay a really important role. And I'm going to be mentioning genetic testing a lot of the time. It's if you are genetic heart disease, we actually understand the genomics better and better. And so this is an example of an individual here with you'll see ventricular topic's actually coming from the right ventricle. They've got t wave inversion anteriorly and this is a rhythmogenic Ventricular myopathy And they've actually presented with a VTE from the left. They have left ventricular involvement as well, which is classical nowadays for arrythmogenic cardiomyopathy. And then we'll go on and do a cardiac MRI. I don't think that's projecting particularly well. But on the on the left side you'll see an enlargement of the right ventricle there with a distortion in the outline of the right ventricle indicating aneurysms in the wall and then scarring over here on in the in the left ventricle. And this will be picked up predominately by MRI rather than by echo. What about electrical heart disease? And that's ion channelopathy. That is another term for that long QT syndrome is the one you've probably most heard of. The most famous of the electrical heart diseases since was the first to be described and a range of tests is ECG echo just to make sure that you're not missing a phenocopy. Something that may be causing prolongation, but is actually due to structural heart disease, exercise, testing and ambulatory monitoring and really help with diagnosis and risk stratification. Genetic testing is so useful here as well in terms of making diagnosis and supporting investigation. And so here we've got an example of a patient with big peaked T waves, broad based t waves QT prolongation corrected for heart rate giving of a massive QTC. But many of these patients have much more subtle subtle changes in the QT interval that are less straightforward to diagnose, particularly when you start to look at families rather than the incidence cases that have caused cardiac arrest or sudden death. And just a reminder of some of the normal ranges over there. Now, this unfortunately hasn't projected well, but you can see it's poorly controlled epilepsy. So this is little vignette had a young woman in her early twenties had a long history of poorly controlled epilepsy and she'd never really had an ECG done. She'd seen lots of neurologists and she wasn't responding to multiple types of antiepilectic medication. You'll see that there are some changes here on the ECG, some T wave changes anteriorly, which are not ones that we would generally try to dismiss out of hand. And laterally, particularly the QT intervals starting to look quite long. You can't really see the end of the t wave defined very well. Um, implanted a loop recorder in her just to make sure because I was making the diagnosis and about a week later we got that anyway as a cause of her epilepsy. And in fact she responded incredibly well to beta blockers and and is done fantastically without the need for an ICD. And in fact, many of these patients can be managed very well with medical therapy rather than resorting to highly invasive treatments. Now, one of the other conditions that I look after is Brugada syndrome. As Steve mentioned, Brugada syndrome is another condition that predominately affects young male adults. And in fact, as you'll see in a moment, is probably probably the major cause for young, SADS deaths. These are these sudden deaths without any evidence of heart disease. And we diagnose that with a range of tests. And the Brugada syndrome is manifest in the right ventricular outflow tract, which is not always covered properly by the ECG. So we have to do particularly extensive and specialist EKGs to make diagnoses and to do this stratification. And sometimes you even have to do provocation testing with sodium channel blockers. And this is a particular one called ajmaline. You may never have heard of that. It's it's one that we use as a short acting intravenous drug. And again, genetic testing can play a role. But this is an ECG that if you saw an A&E, you'd think this person's having an acute MI. And you're right to want to exclude that first. But this is actually a cardiac arrest survivor who was 18 years old and had this pattern in v1v2 of this j point, and ST elevation with a curved pattern that's typical for brugada symptom called the type one pattern. And this is his brother who we saw a few weeks later where he had this ajmaline provocation test. And after 3 minutes of having an intravenous sitting channel blocker, he gets exactly the same pattern. So he's a carrier for the same condition and at risk of sudden death, although thankfully not quite as severe as his brother's. There's one other condition that you probably need to know about, but if you do come across it, it's going to be unusual because it's present in about one in 10,000 people, and usually in children. In fact, it's probably the most common cause for sudden cardiac death in children. Usually the child who's running in the playground and collapses and dies suddenly, particularly tragic conditions catecholamines polymorphic ventricular tachycardia, and we diagnose it with exercise testing, a Holter monitoring. But obviously most children, it's quite a challenge to do that. But there will be adults as well who are affected by it and carriers and they can pass it on to other family members and genetic testing is very good again for making the diagnosis and often the ECGs completely normal. You would never suspect that maybe bradycardia for age. And then when they exercise, they get a complex ventricular to be bidirectional, like to be polymorphic. Ventricular tachycardia is what ensues and then ventricular fibrillation. And this one thankfully terminated by a shock. And so this is one where we always say to any GP or neurologist who listen or can hear it is when you if you have a seizure running, that's not epilepsy, that's cardiac until proven otherwise. So any seizure during exertion is not a seizure, it's not neurological, is cardiac. And particularly in children. Just be aware of that because in our series of cases of sudden deaths, that was a one heralding factor that could have been preventable. So SADs where we have a sudden death with a normal coroner's autopsy, normal toxicology. So therefore, normal heart and is is unexplained. We suspect that we're going to find these electrical heart conditions and indeed, sometimes genetic testing will make that diagnosis for you. And we do a wide range of tests in family members, including MRI and ajmaline testing where needed and genetic testing. If we find something suspicious in the family. And if we do that process, if we go through that process, this is some data from back in 2018. This is the largest series reported so far, and it's from our group. We actually find that around just over 40%. So in this series, 42% of families, we have evidence of genetic heart disease, in particular the Brugada syndrome being the most common diagnosis. And most of these cases are of sudden deaths, young males dying in their sleep, which is the characteristic of Brugada syndrome. But we've got lots of these other conditions, including even Cardiomyopathies being detected in families, even when the autopsy has proven normal in the best of hands. But there's still this group of families where we don't find a cause and with genetic testing doesn't seem to get us anywhere. And this is where our research is directed to try and understand with that what is causing the sudden deaths in these individuals, because in the end, we want to prevent them. What about an athlete's? Well, they also have a a a risk of sudden death. And often those risk that risk of sudden death isn't necessarily related to their exercise. It's actually it often occurs when they're not exercising. So just to be aware that while there's a higher rate of exertional sudden death in athletes, actually their risk isn't necessarily always related to exercise, but we still see the normal heart, the electrical heart conditions being important and relative irrelevant in these conditions. But cardiomyopathy tends to take up a bigger slice of the pie than in other and then in non-athletes. And what is the risk of being an athlete? Well, it's about a relative risk of 2.5 higher risk of cardiac arrest than in more sedentary individuals. And this is data from the Italians. They put in a a programme of pre participation screening for individuals 14 years and older. It's controversial. There are many antagonists and many protagonists. It's not funded in the UK, but as you say, it's funded initially and it's really galvanised when we have these high profile sudden deaths that I've mentioned to you already, the screening process and that's been adopted in Italy and is adopted by some of the screening organisations, the charities in the UK is to do the family history physical examination and a resting ECG as a screening tool in the US. Traditionally it's stopped the physical examination and family history without going onto the ECG, but there are changes afoot in the US as well. But if you have positive findings then you go on to screen. You may be missing still cases. There, but if there are positive findings, there will be potential findings of cardiovascular disease that could be managed. And according to the diagnosis and some will be able to return to competition, but some won't. There are still going to be individuals who are having further examinations who have basically false positives in the screening process, and that's something that people have to be aware of when they go through any screening process. And they're asymptomatic individuals who would otherwise be not aware that they have a risk. And this is endorsed by the ESC, the International Olympic Committee, C four and with the other sporting organisations, including the RFU, etc., and slowly being taken on by others, but not by the screening committee in the UK. And this is historic of this is data from Italy showing the impact on athletes and non athletes for the screening over time. So it's a historical control. So not a case control study, but still giving some evidence for the reduction in risk over time. And that's probably the best study we have at the moment. Finally, suspicious syncope. So obviously we need to interpret syncope as to whether it's phase vagal or whether it's cardiac syncope with a more abrupt onset and offset. And sometimes that's going to be very difficult to understand. But often we may see evidence of hypoxic convulsions and seizures being the the pathway for diagnosis. Again, neurologists and cardiologists need to work together from that point of view, we can do things like tilt testing. We look at blood pressure response and heart rate response to tilting and to GTN provocation. This is a normal response and here you'll see the blood pressure and heart rate drop in response to just tilting without even the need to GTN and all this an old fashioned tool and it has its faults. I still use it for for examining the the symptomatic correlations in patients who symptoms who are reporting unexplained syncope. But of course just must remember that we don't forget to do an ECG even if you're suspicious, if you're vaguely suspicious that it's face a vasal vagal rather than others. Complete heart. BLOCK of Parkinson white syndrome. As excited as can cause and can cause cardiac arrest and syncope as well. So always be aware that there are acquired causes that may be doing so, not just a genetic. Thank you very much.