Peter Backx transcript

Written by Christopher Kelly

May 4, 2017


Christopher Kelly:    Before we get into this week’s interview with Dr Peter Backx, I wanted to mention that I found Dr John Mandrola’s book The Haywire Heart very helpful in preparing for this interview. Dr Mandrola also has a fantastic blog. I will link to both the book and the blog in the show notes for this episode. I also wanted to let you know that Fat Fibre Version 2 is now available. “What the heck is Fat Fibre?” I hear you say. Well, in an attempt to make a hypoallergenic MCT oil powder that doesn’t contain high GI carbohydrates or sweeteners, we created Fat Fibre.

The aim was to design something that we wanted ourselves but wasn’t available on the market. A powdered MCT oil that could be used as fuel during races and didn’t because GI distress. Many of our clients tried Fat Fibre and the feedback was overwhelmingly positive. More importantly, we wanted to know exactly what Fat Fibre was doing to glucose, ketones and insulin. So we tested those metrics in a group of nutrition geeks, scientists and low-carb elite athletes.

The resulting data was recently published in a peer review journal and that led to an even better iteration of Fat Fibre, which is now available on sale. Find it over at, link is in the show notes. Now on to the interview. Hello and welcome to the Nourish Balance Thrive podcast. My name is Christopher Kelly and today I am joined by Dr Peter Backx. Hi Peter.

Dr Peter Backx:    Hello, hello Chris.

Chris:    Thank you so much for being with me today. Peter is a senior scientist at the Toronto General Hospital research institute. Peter, can you talk a little bit about your research and why you do it?

Peter:    Yeah my research, I’ve been doing research since the sort of late 80 in the area of heart failure and heart disease. And my current research has evolved over the years to our primary focus now being on atrial arrhythmias and specifically atrial fibrillation in relationship to endurance exercise.

Chris:    Interesting. Okay and can you talk about…so one of the things that I think makes you most interesting is you are both endurance athlete and you are a research scientist that knows so much about your particular situation, and you’re a patient. So can you talk about the type of sports that you enjoy?

Peter:    Yeah so I enjoy a lot of sports, but the ones I believe I excel in over the years have been soccer and hockey. Being raised on a farm in southern Ontario, those are the 2 sports that really were the ones that most young men participated in and I was one of those and continues to play it. I played competitively in both sports and I continue to play to this day. And yeah so it’s interesting about you pointing out that I’m also a patient. So as time has gone on, I’ve actually developed atrial fibrillation myself and I believe that I guess about 10 years ago, I started to suspect that there might be a relationship between my endurance sport activities and condition.

Chris:    Can you describe what a-fib is? Because a lot of people listening won’t know, myself included. So there’s lots of different types of arrhythmias and a-fib is just one type. So could you describe what it is?

Peter:    Yeah so to give you a little bit of background before discussing the specifics of atrial fibrillation, what you need to appreciate is that the heart itself has its own electrical system, very much like a car. The sparks of a car drive the burning of the fuel and that’s done at a very coordinated fashion as the cylinders fire in sequence. In the heart, the heart has this intrinsic electrical system that really does serve sort of the same purpose. It’s got a spontaneous beating rate that’s intrinsic to the heart.

And then there’s control systems that come from the brain and then some other tissues can release factors as well that can modulate that intrinsic activity. So if you break that down a little bit further, the way it works is that this signal begins – is driven, it’s like the generator I guess is what you might call it. The spontaneous generator starts in a region called the sinoatrial node. It’s actually located strategically at the junction of the atria, which are the upper chambers of the heart, and the veins that bring blood back from the body to the heart.

And we don’t need to get into the details of why nature might have put it there, but that’s where it resides. And so the electrical signal emulates from there, goes to the atria, causes the atria to contract, which then the signal continues after a delay and goes down into the ventricles of the heart which is really the big pumps that pump the blood to the lungs and to the systemic – to the entire body. And once that signal gets to the ventricle, it contracts. Now what happens in atrial fibrillation is that sequence is disrupted.

So rather than the SA node –the control centre really controlling the intrinsic beating rate of the heart – what happens is that the atria actually take over. And the reason they take over is because they undergo – due to what we call remodelling. So there’s changes in the structure and in the electrical function of the atrial cells themselves that lead to almost a stochastic or random electrical behaviour within the atria themselves. And so the consequence of that, it turns out, is that you get very, very rapid electrical repetitive simulation of the atria in a chaotic fashion. And now those signals go down into the ventricle at a much, much more rapid rate.


Peter:    So I’m not sure if that….maybe I’ll stop there, but you end up…the net result of this is that the atria really don’t contract any longer. They just provide these random electrical signals down into the ventricle. And the ventricles, rather than beating at about 60 beats per minute –which is what a typical human male and female, their beating rates would normally be in terms of the pumping repetity or the pumping period –it’ll actually go up to around 120 to 140 times per minute and also be somewhat quite random in terms of how they’re initiated.

Chris:    How did you know that this was happening for you?

Peter:    Well in my case – and I think it’s true in most endurance athletes that develop atrial fibrillation –there’s no mistaking when it actually happens. The reason is because normally – as you know, being an athlete yourself – when you engage in any endurance activity or any increase in physical activity, your heart rate goes up. It’s go from 60, a trained athlete – a young trained athlete can take that heart rate up to 200, maybe even a little bit above that. But it’s very organized in terms of how that increase actually takes place under normal circumstances.

When you get atrial fibrillation, you can have heart rates or beating rates of the ventricles – as I already mentioned, there can be 120, 130, 140 – they’re very disorganized and it’s not done in a manner that leads to a large increase in blood output by the heart itself. So the next consequences that you actually will often get a reduction in blood pressure and you won’t feel well. I mean you’ll feel…some people will feel palpitations but the main thing – the main symptom that individuals will have – will be fatigue and they just won’t feel very good. They maybe might feel a little bit dizzy and tired.

Chris:    That just sounds like…I mean you might just feel a little bit like that after a training session anyway, wouldn’t you agree?

Peter:    Sure but if you were on your bike or you’re playing a hockey game or soccer game, you would have this fatigue while having essentially very little work output.

Chris:    Right, okay.

Peter:    Just the slightest bit of increased demand placed on your body would very quickly match the ability of the heart to actually pump the blood. Your performance would just plummet. And the very first time – by the way – that it happened to me, was in a hockey game. And I knew immediately because I couldn’t even skate from one blue line to the other without actually being quite tired.

I went to the bench, took my pulse and realized something was going on. I didn’t know what it was and later got diagnosed. But that’s very often what happens, is someone will be in the sport or…it happens actually very frequently after competing or after doing your exercise. It’s somewhat more common for it to occur during that period, although a substantial number of athletes, they actually have atrial fibrillation induced by the exercise itself.

Chris:    Okay. What was that like for you, having such tremendous knowledge of the biochemistry and physiology of the heart and something like this actually happening to you? Like having such tremendous insight into your personal situation, what was that like?

Peter:    Well I knew immediately that I had a heart issue, by taking my pulse. Having been trained as an electro cardiac electrophysiologist, I immediately started to do the rule outs. And some of the rule outs were actually quite daunting. If I had had a ventricular arrhythmia, that’s the kind of situation where you have a sudden cardiac death that you see tragically in some sports – an athlete will fall over. And if there’s not a defibrillator present in short order, that individual almost always will either die or suffer some serious damage to the heart and brain.

In my case, it was atrial fibrillation. So it’s actually very, very common and I wouldn’t call it benign. But relative to ventricular arrhythmia, it certainly is much less serious. And that was the first thing that came to my mind, was “Oh my gosh I might actually have a ventricular tachycardia or tachyarrhythmia which would be far more serious.” But even knowing my age and by the time I actually left the rink, I had already started to deduce that it was probably an atrial arrhythmia, just because it’s such a common arrhythmia.

Chris:    Okay. And how dangerous is this situation then, compared to like a heart attack? Is it very dangerous situation?


Peter:    Well I would say generally speaking, if it’s your first bout for example, it’s not really dangerous outside of maybe you fainting, losing your composure and if you’re in…let’s say cycling, you might actually faint or have a fainting spell. You could injure yourself that way. Now it’s not to say there aren’t side effects that are more related to this sort of biology, because you can develop things like strokes but they generally don’t occur without sort of persistent and prolonged atrial fibrillation.

    There are a number of consequences but usually there’s acute episodes which we refer to as paroxysmal atrial fibrillation. Those other than the sort of reduced performance athletically, beyond that it’s relatively benign. The real problem is that it’s an indicator and once you’ve had one episode, it’s really indicative of where you’re headed. Once you have one episode, you’re almost certain to have more episodes. And in the field, we actually use a term called ‘AF begets AF.’

What that means is atrial fibrillation – once you’ve had a bout, it actually promotes changes within the atria that actually promote further changes that then lead to the promotion of the arrhythmia itself. So that’s why in the research that I’m doing now, we’re trying to understand how to break that vicious cycle that actually occurs in most patients that actually develop atrial fibrillation. And what I just said is not true for everyone, but it’s certainly true for the majority of individuals that get atrial fibrillation.

Chris:    Talk about the risk factor of endurance exercise. So I listen to Dr Mark Cucuzzella who is a professor of family medicine, and Tommy who is someone I work with and he’s also a PhD research scientist. And he talked about how the greatest risk is if you’re averaging more than an hour of endurance exercise every day for 20 years. Would you agree with that statement or is there a risk associated with all endurance activity?

Peter:    I think the jury is still out, actually. If you look at the small trials that have been done, they’ve been done with very specific types of sports. So to be able to generalize to all different kinds of sports, I think we don’t really have enough data. When it’s been looked at though in these trials, it’s very interesting that the majority of people…so let me just back up for a moment and say the biggest risk factor for developing atrial fibrillation is aging. By the time you get to 70 years of age, about 10% of males and around 8% or so of females will develop atrial fibrillation.

    Now having said that, the other risk factors…endurance exercise is something that’s been discovered very recently as a risk factor for atrial fibrillation. Historically, what’s always been strongly associated with atrial fibrillation is the other end of the spectrum relative to endurance sport and fitness. Obesity, diabetes, heart disease, hypertension – all the sort of risk factors for cardiovascular disease, which are almost always reduced substantially by exercise, are also strong predictors for atrial fibrillation. In fact your risk is you have about a 5 fold higher risk if you have certain kinds of cardiovascular disease of getting atrial fibrillation as you age relative to the general population.

It’s a long winded way of actually answering your question but when we looked at various endurance sports, it’s quite interesting that the risk – the relative risk – of developing atrial fibrillation in individuals that are…and these are really high end athletes now that we’re talking about, so much greater participation or engagement than you just described. They all have a risk factor that’s actually quite comparable, as far as we can tell. So they also have a sort of 5 to 10 fold increase in likelihood of developing atrial fibrillation. So it’s a spectrum.

So as you drop off from the really high end athletes where this has been looked at – in orienteering, in cyclists and in particular – so the numbers, we really don’t know. We don’t know whether this is a threshold phenomenon or whether it’s just a gradual…this is the kind of research that we’re actually engaged in now. We’re trying to understand precisely that question actually. Whether there is a threshold or whether this is a gradual dose dependent effect that you can actually have on the atria.

Chris:    And one other thing that Dr Mark Cucuzzella said in that same interview is that athletes do not have a high rate of the dangerous ventricular arrhythmia that you talked about earlier, where someone might just drop dead. Do you think that’s true?


Peter:    Well that’s also a little bit controversial, actually. There certainly are research groups around the world who have identified remodelling – so changes within the ventricle also associated with endurance sport. And again, these are typically the studies have been done on individuals who are either Olympic athletes or people who are engaged in the very high end of their sport. There’s been post-mortem data to suggest that indeed, individuals that have been competing at very high levels in endurance sport have an increased level of changes that are certainly not what you would want as changes within your ventricle.

So there certainly is evidence that changes occur on the ventricle as well, albeit that evidence is much weaker than it is in atrial changes that actually occur. But I think there’s little question that both chambers – atria and ventricle – are affected by exercise. But the sensitivity is much different between the 2 chambers, atria being far more sensitive to the effects of endurance sport than are the ventricles. So I think in that sense, his name was Tom you said?

Chris:    Yes, yes. Tommy.

Peter:    I think he’s correct in stating that the effects are certainly much less than in the atria and there are lots of people who certainly believe what he does, and that is that there’s nothing but benefit from exercise. But I recaution to say that there certainly are studies to argue that and to support the idea that there can be some changes that actually occur. Now having said that – and this also relates to atrial fibrillation – if you actually look at the percentage of people who get the disorder – atrial fibrillation or even ventricular changes – it’s actually a very small percentage.

    So what a lot of people are speculating about in the field is that there are genetic predispositions for individuals developing these kinds of changes. For example in the case of ventricular changes, there’s a number of genetic mutations that have been associated with right ventricular dysplasia for example. And many of the changes that have been identified in endurance sport have been associated with changes in the right ventricle.

And so there’s been some speculation that those individuals will harbour some kind of genetic predisposition through actually developing changes similar to those that [00:18:01] [indiscernible] frank – individuals that have frank genetic disorders. And the same may very well apply to atrial fibrillation. The percentages are so small that it’s very likely that a certain profile of genetic background may predispose an individual to the changes that actually are associated with endurance sport and the atria.

Chris:    Do you know if it’s possible? Are there any commercially available tests that might tell you whether you were of that genetic predisposition?

Peter:    There certainly are. There are these panels called…where you can look at your exosomes, where you can actually sequence what’s called the coding region of various genes. And most of those genes are genes that have been identified through genetic studies as factors in predisposing to certain kinds of arrhythmias. And that research has been primarily in the area of ventricular arrhythmias but a number of the genetic disorders associated with ventricular arrhythmia are also predisposed to atrial arrhythmia.

And that shouldn’t be too surprising because the majority of those genes are actually encode for proteins that are called ion channels, which are the underlying proteins that produce the electricity within the heart. And so you can certainly do a screen, what’s called a sort of panel and that panel would pick up a number of genes that are known to be linked to early onset atrial fibrillation.

Chris:    Interesting. And then what would you do if you found out that you were of that genetic predisposition? Like do something else, take up weightlifting, something different.

Peter:    Possibly. I mean on the other hand if you don’t do anything as I already said, if you’re on the other end of the spectrum, you’re even more – probably even a bit more vulnerable to developing the disease. So I think the way I would handle it if I knew that I had a genetic predisposition, I’m not sure I would change anything. And the reason I say that is because nowadays if you’ve got health insurance – of course in Canada we have universal healthcare – it’s not hard to be scheduled for what’s referred to as an ablation.


Peter:    And the ablations these days – that’s a procedure where they put a catheter into your heart and they do selective burning or freezing of regions of the heart, of the atria that we know are engaged in setting up that random electrical behaviour or electrical activity. And so those procedures are becoming more and more successful. They’re having fewer and fewer side effects and I think the beauty of developing a condition like this – although it’s never nice to have any sort of health condition – is that it’s very curable. It’s actually…you won’t be able to fix the atria, but certainly prevent the electrical disturbances for actually disrupting your day to day activities.

Chris:    And is that the procedure you had done?

Peter:    Yes it is, yeah.

Chris:    And was it basically a cure for you as it has been for many other people?

Peter:    Yeah it has been a cure for me – knock on wood. I actually had it done exactly 3 years ago, almost to the day actually. And I’ve beaten the odds in some senses because the studies that have examined frequency of recurrence after an ablation show that about 40% or so of patients will actually redevelop some signs or frank atrial fibrillation within about 6 to 8 months. But that data is actually a little bit dated because the procedures as I just mentioned have gotten better and better, and I suspect that those success rates have skyrocketed over recent years.

Partly because of the training of the physicians, but also the companies that are engaged in producing catheters for ablation have developed this very sophisticated mapping systems and other technologies that actually have increased the success rate of the actual procedures themselves and certainly have reduced the reoccurrence rates following a procedure.

Chris:    At this point I should credit Mark Federman, who’s a client of ours and very competitive cyclist, who both introduced me to Dr Backx and had some fantastic questions that he shared with me. so I think if I asked some of Mark’s questions here, I’ll get to the – excuse the pun – the heart of it, because I’ve not been affected personally. I don’t think I can ask as good a questions as Mark did. And Mark also had the ablation procedure but his main question was if he keeps doing the same thing, will that lead him right back to a-fib or is the problem cured for life? So could you answer that question?

Peter:    Sure. So there’s no question that if he continues to engage in endurance sport, he’s going to continue to promote atrial changes that actually were initiated – in all likelihood – from the endurance sport to begin with. Having said that, the ablation procedure itself should be able to – if done successfully – actually control future events and be able to suppress future bouts of atrial fibrillation. I think the other aspect to this that is always of some interest is that as you age, you’re going to succumb to something.

And what’s very interesting is that even though individuals involved in endurance sports will develop atrial fibrillation and to some extent some ventricular changes, the data shows that the more exercise you do is the longer you live. And of course, there’s going to be some individuals who may have an acute episode and have sudden cardiac death. I mean those are tragic events but if you take a population of people and you’re asked the question “Who lives longer?” the answer is very clear. The more sport you engage in – the more you do it – is the longer you live.

Chris:    Right. So do you think it’s trying to find that sweet spot then? Do you think it might be some endurance athletes are over-exercising to the point where they’re making pathological changes to their heart, and then there’s a whole probably much bigger group of people who are completely sedentary. Do you think that’s right? Do you think it’s really about finding that sweet spot?

Peter:    I think it is. The problem is we don’t know enough to know where that sweet spot is.

Chris:    Goddamnit, that was going to be my next question.

Peter:    And in all likelihood, the sweet spot actually varies from person to person and I alerted to the genetic predisposition in certain individuals, and I think with those kinds of complexities, we’re really at our infancy in terms of understanding the question that you’re driving at. We don’t have any guidelines, we don’t really know which individuals are going to develop.

And even individuals who don’t engage in sport and don’t have heart disease, as they age…now that’s a smaller fraction of the population – will still nevertheless actually develop atrial fibrillation. So in those individuals, we don’t know what the predispose or the causes are. But again in all likelihood, we’re dealing with a spectrum of different genetic backgrounds. And the outcome of those genetic backgrounds depend on the activities that those individuals engage in.


Chris:    Do you think that the intensity of the exercise is important? So one of the things that Dr Mark said in that same interview was that he thought that most runners were running too hard, and I’ve said certainly been there with my endurance training. I’ve had tremendous benefit from slowing down. So your default approach to the exercise in most people is that you’re going really hard. Like you want to ride around with your heart rate at 180 beats all the time. But actually if you slow down and you ride around with 140 beats – to me as a 41 year old male – it seems like it’s not enough stimulus to get faster but in the end, it is. And then you just save the intensity for when you really need to use it, like in a race.

    So in the literature, this approach is described as a polarized approach to training. And we might think that might have tremendous benefit, both in terms of not just longevity but also wellbeing. Like people generally feel much better when they take a polarized approach. But do you think that has any relationship to a-fib? Do you think the intensity might be important?

Peter:    Yeah I think certainly…now here’s where I can actually say a few things relatively more definitively. So that’s actually one of the first questions, Chris, that we actually tried to address with our research. And the way we did this of course – mice are not humans, our studies are on mice. And we actually engage the mice in swimming and free wheel running exercise and we measured things like oxygen consumption rates.

The first interesting thing that I’ll tell you just before I give you the direct answer to your question is that the ability of the mice to actually exercise – the intensity with which they will exercise – is somewhere in the range of about one-third to one-quarter of what a human can drive himself or herself to do. Of course they’re not necessarily motivated to make the Olympics, in the case of a mouse.

Chris:    They’re not competitive.

Peter:    Right. So that created a bit of a problem for us, and so we wanted to answer the question exactly that you asked. So what we end up finding out is that once we’ve trained the mice and allowed them to acclimatize to a free wheel for running, we actually started to then put resistance onto that wheel. And what’s remarkable is that if you allow a mouse to just use a free wheel ad lib with not very much resistance on that wheel, they will get atrial changes but they will not get the atrial changes that we know are associated ultimately with the development of persistent atrial fibrillation.

And specifically that involved fibrosis of the…so that means replacement of some of the muscle of the atria with connective tissue, like the stuff you have in your bones and your tendons. And what we found is that when we put resistance onto the wheel, indeed under those circumstances the mice actually do develop fibrosis in the atria. So that demonstrates – to me at least – that there is a threshold to the activity in a mouse.

So coming to your…the different kinds of training regimes – almost certainly if you’re going all out all the time, it’s like an integral. If you integrate that behaviour over a long period of time, I think it’s inevitable that that’s going to drive far more adverse changes in the atria than if you take a more leisurely approach with your exercise. And maybe reserve the real intense exercise for the competitions.

Chris:    Would it be possible to study that in humans?

Peter:    For sure, I would think so. But I mean, the percentage of individuals getting these conditions is again relatively low, so you need a large population of athletes to do this and you’d want to almost be doing it in somewhat older patients. But remember Chris that these changes that are happening are occurring over years. So the only way that I could think a study like that could be done would be to track a huge number of athletes over a long period of time, because only over that – let’s say starting from your 30s or something like that. Most people – even endurance athletes that go on to develop atrial fibrillation – are typically not developing this condition until they’re in their mid-40s. And that’s very early, relative to most of the population. And the majority of them will only develop them as they age.


Peter:    So certainly I think those kinds of studies are doable, it’s just that they’re formidable in terms of whether there could be enough resources available to actually carry out that kind of a study to answer that specific question.

Chris:    And would you think that you would expect to see the same thing in humans as you did in mice? So I know that rodent studies are…you need to know your rodent before you can really say whether it’s going to translate into humans or not. I know there’s many nuances for rodent studies and I’m sure you’re very much acquainted to those. If I had to force you to put money on it, would you expect the same thing to translate into humans?

Peter:    I do and the reason is because the changes that we actually see in the mouse are exactly the same changes we see in humans as well as other species. So this effect of exercise and the way exercise impacts on overall health as well as heart health, is really similar across all species. And I don’t think that should be too surprising because of the nature of certainly mammals. If you look at evolution – if you believe in evolution.

Chris:    I do.

Peter:    Well [00:31:22] [indiscernible]. But regardless, life systems are based on predatory-prey activities if you look in nature, whether you believe that’s evolutionary or not. And so nature has already developed that very refined system for being able to change your level of activity over a broad range. And I think humans and mice fit into that overall paradigm.

Chris:    Okay, very interesting. Let’s talk about inflammation, because Mark had another really great question here about inflammation. Do you think that somebody that’s walking around with a buzz or chronic level of inflammation may be at greater risk? Perhaps you’d done a high sensitivity C-reactive protein blood test and it was 5 or 6 or 7 – which I think most people agree is quite high. And that level of inflammation may be being caused by something that’s totally unconnected to anything that’s going on with your heart. Perhaps it was an undiagnosed food sensitivity or a chronic infection. Do you think that would contribute to a-fib?

Peter:    So I don’t know the answer specifically for that question except to say that a number of inflammatory conditions – like rheumatoid arthritis being one and several others – certainly there is increased likelihood of individuals suffering from those chronic inflammatory conditions to also have cardiovascular conditions, and that includes atrial fibrillation. So there’s a couple of recent papers to suggest that there is a link in fact with the systemic kind of inflammation and the likelihood of developing various types of cardiovascular disease, although the majority of those are actually coronary artery disease which then would lead to a heart attack.

Now having said that, what’s interesting though about heart disease in general and certainly atrial fibrillation as well is that these are inflammatory conditions. So atrial fibrillation –these are studies now that have gone back at least 10 years in humans – it’s very clear that an atria that’s been in chronic atrial fibrillation – and that means from months to years – has lots of signs of inflammation. And this is again where I think one of the reasons that I have some faith in our rodent model is because the main factors that we’ve actually found to be linked to the atrial remodelling with exercise and the mice are in fact inflammatory factors.

And the primary one that we’ve actually been focusing on is kind of like a master regulator of inflammation – a molecule called tissue necrosis factor alpha, or TNF alpha. It actually drives the production of a number of other cytokines, inflammatory cytokines. And this particular molecule is of interest because it’s actually a mechanal sensor in some tissues. So it actually is engaged in sensing mechanical changes. And we think that’s actually the link. So we think that we’ve hit on to sort of the link between mechanical stress on the heart and the inflammatory elements that we know are critical for – or certainly associated with, I should say – with atrial fibrillation.

Chris:    And what happens if you try and inhibit the TNF?

Peter:    So in our mice when we’ve done this – we’ve done this in several different ways. We can completely project all the atrial changes from certainly the atrial remodelling wherein we see the fibrosis is completely prevented and we can no longer induce atrial fibrillation in our mice if we block TNF from signalling. We actually did it in 3 different ways – 4 different ways, actually. One is we have a genetic knockout of the TNF alpha. We’ve recently actually done what we refer to as a tissue specific, so we can actually knock out…

We can take the gene out of commission in a variety, in a selected cell type, in a selected tissue. So we managed to be able to do that actually in the muscle cells of the atria. Those studies, I don’t have all the details on yet. But if you knock the gene out in the body, in fact we cannot get the atrial changes associated with exercise.


Peter:    And then there’s the common drug called Etanercept. It’s actually a large molecule that needs to be injected into individuals, it’s commonly used in rheumatoid arthritis, inflammatory bowel disease and a number of other inflammatory conditions. And that also was extremely effective in our mice. And then we also have a new drug called XPro, which is a more targeted, much more specific molecule for knocking out TNF alpha, and that also has been effective in our hands in the mice.

Chris:    Just to clarify, you said tissue necrosis factor alpha and I was familiar with tumour necrosis factor alpha. Are we talking about the same molecule?

Peter:    Yeah, tumour necrosis. Yeah. It’s discovered by…sorry, I misspoke there. Yeah I mean it was discovered by immunologists and cancer people and it’s turned out to play an important role in many, many diseases – inflammatory diseases, etc.

Chris:    Yeah I am familiar and I wish it was cheaper as a blood test. It’s commercially available but it is quite expensive. You can make your regular blood panel quite expensive if you start adding on too many markers like that, but it would be really interesting to look at on a more regular basis, I think.

Peter:    Chris you know one thing about considering doing that is that we tried to look at TNF alpha serum levels in our exercised mice, and we could not detect. And so that’s why we think many of the changes that are actually happening are very specific to the atria themselves and the cells within the atria.

Chris:    That’s really interesting and do you think that if you were to inhibit TNF alpha, would it blunt the response to training? Like do these mice get fitter?

Peter:    You’re asking some great questions.

Chris:    Thank you.

Peter:    We published our first study in Nature Communications about a year ago and we made a strong point of emphasizing that in fact our treatments did not reduce in any way the positive physiological benefits of exercise. So all the things that we know are beneficial in terms of ventricular function were all maintained in the presence of TNF alpha inhibition. Because obviously if you’re going to take a drug that reduces your performance, obviously that’s a non-starter. I’m not sure that I would recommend taking TNF alpha antagonist even with the beneficial effects being maintained in the ventricle, but the bottom line is that this did not interfere with any of the other perimeters –at least that we looked at in terms of the effects of exercise on the heart.

Chris:    Well isn’t that curious then? It does make you wonder what the heck is TNF alpha for? Why does this happen with exercise?

Peter:    Well if you want, I can speculate.

Chris:    Yes of course. I know that scientists often need a little bit of persuasion before they’ll speculate but I would encourage you to do so.

Peter:    Yeah we actually – and this is really what gets me up in the morning – is I think we’ve actually hit on a role of this molecule that’s been sort of overlooked in the past. And a colleague of mine by the name of Dr Sebastian Bolz – he was a vascular physiologist at the University of Toronto in the department of physiology. And he’s just published a paper where they’ve shown very definitively, there’s something called a myogenic response in the vasculature.

Now this is a response of the blood vessels – the very, very small blood vessels that are controlling the blood flow to the capillaries, which is where all the nutrient exchange actually takes place between the blood and the tissues. And they’ve been able to show that if you acutely interfere with TNF ALPHA signalling, you completely lose the myogenic response. And that means that you reduce the ability to actually regulate local blood flow within tissues.

And it’s interesting because if you look at people who have conditions, whose TNF ALPHA is actually elevated – some of the problems you run into are actually vascular, blood pressure related. And he is of the belief that this may explain why trials with TNF ALPHA inhibitors have actually failed, because trials that have been used to prevent inflammation in the heart for example, those trials turned out to be failures in terms of providing benefit.


Peter:    And he’s of the belief that acutely, the application of these were actually causing adverse events. But it comes to the sort of root of what the TNF ALPHA molecule does. We know it’s an inflammatory factor, we know it’s very important in the immune cells and in particular macro [00:40:35] [indiscernible]. But this is one of these molecules that seems to have a very diverse range of activities. And I mentioned before that we believed that this is acting as a mechanical sensor, very similar in these resistance vessels was acting as a mechanical sensor. And then the question becomes why would you have a mechanical sensor actually sitting in the atria?

I’m not sure if you’re familiar and some of your audience may be familiar with this, but the atria is not only a muscle chamber, but it’s also an endocrine organ. It’s very much engaged and involved in the regulation of your fluid volume in your body, and the fluid volume is regulated by a factor which is called atrial natriuretic factor. It’s actually produced by the atria and it’s released during periods when you have elevations in the pressure in the atria or essentially when you have elevated fluid volume within your body.

And so we think – this is where I’m speculating now – I think that the TNF alpha may be a factor in the stretch mediated regulation of the endocrine function within the atria and alternatively, no organ and no tissue would probably benefit from excessive stretch. And when you exercise…every single time you get on your bike or you exercise intensely, the back pressure on your heart goes up very, very substantially.

It’s like your venous pressure is normally sitting at 0 to 2 millimetres of mercury relative to the outside, and when you exercise, those numbers can go up as high as 30 millimetres of mercury which can certainly…we know has an enormous impact on stretching of the atria. And so this may be also a protective mechanism to sort of prevent overstretching of the atria.

Chris:    Okay I’m following you. This is absolutely amazing, fascinating stuff. Talk to me about alcohol and a-fib, and how the two might be connected.

Peter:    Yeah that’s a great question as well because I happen to be a person who always enjoyed my one or two pints after a soccer game.

Chris:    What athlete doesn’t, right? It’s deeply engrained into cycling culture as Mark pointed out – attending these cycle cross races and competing in cycle cross races. And some of the guys, they’ve got a beer in their hands before I’ve even crossed the finishing line. They’ve got onto the podium and they’ve got a beer on before I’ve even finished – absolutely incredible. But it is deeply engrained into athletic culture. Sorry, go on.

Peter:    No absolutely. And part of it is rehydrating but I think there’s a bit more to it than that.

Chris:    Yeah for sure.

Peter:    And the thing about it is that one of the other changes that we haven’t touched on this yet – one of the other changes that actually happens in the heart and the way the heart is regulated by exercise – is you get a change in what’s called the autonomic nervous system. And I think Chris you’re very aware an athlete’s heart rate is almost always considerable lower than that of the general population. Now there’s a bit of controversy as to what primarily drives that, but I think most people agree that it comes almost exclusively from changes in the neuronal inputs to the heart, that are sort of controlling that SA node.

The nerves release factors that change the intrinsic firing rates. And with exercise, the autonomic nervous system changes in such a way that there’s actually a slowing of the intrinsic firing of the SA node and therefore, the heartbeat. And alcohol could affect the heart directly, but we’ve actually done some studies related to this and found that all the changes that actually…that we could detect that occurred in response to – now these again were in mice.

We didn’t get them to drink but we actually lavaged them with alcohol. In that case, almost all the effects seemed to be going through the brain and we thought we were really on to something here because we didn’t know that this had necessarily ever been looked at before. And my student at the time actually went back…I said to him – he’s a summer student – I said “You know someone has to have done this before.”

Because we saw such clear effects which were mediated through the autonomic nervous system. And so sure enough in the 50s and 60s, outside of the Medline era, we didn’t have easy access to these papers. All the stuff had been worked out quite some time ago and alcohol has a very well defined set of molecular targets within the brain and it actually has a tendency to act as both a depressant and a stimulant, depending – and we all know this – depending on the dose.


Peter:    Low dose alcohol is actually stimulatory and that’s exactly what we found, was that it changed autonomic nervous system in a way that actually was very stimulatory at high doses. We didn’t really do that high dose but we know that that becomes a much more…alcohol is much more of a depressant under those conditions. So in answer to your question, the alcohol certainly impacts on the heart but I think it’s primarily – at least our limited research that we’ve done in this and the research that was done previously suggest that most of that is actually due to direct effects on the brain and indirectly affecting the heart.

Chris:    And what did you do when you found out you had a-fib? You stopped drinking completely?

Peter:    Yes I did. I did not drink for I think about 4 years, and the reason I did it – not because I was trying to prevent it, it’s that I had to because almost every time that I engaged in having…particularly wine. I’d have 2 glasses of wine and I would be in atrial fibrillation within a couple of hours, almost invariably.

Chris:    Wow yeah that is some good feedback. Wouldn’t it be nice if everything gave us feedback like that?

Peter:    Yeah but not everyone is sensitive like that. It seems to vary from person to person, just some people get their bouts – I mentioned this before – during their exercise. Lots of other people get it after a large meal and when they go to bed at night. As the condition progresses, I think almost any trigger will be enough to set off an event and so it may be the stage of disease for [00:47:24] [indiscernible] when you actually see it.

Chris:    And do you think the same is true of caffeine? So I think the answer to this is quite surprising, I think there’s actually no connection with a-fib and caffeine – at least not as seen in the data in the literature but do you think that’s true?

Peter:    Yeah all the data’s pretty clear, it’s not increasing the incidents. Having said that, what almost invariably, an episode of paroxysmal arrhythmias – that means atrial fibrillation – that means you’re in sinus rhythm, you’re breathing very regularly and now you suddenly develop the conditions for atrial fibrillation. The mechanism of that varies from person to person but in the majority of individuals, it actually arises because…the belief is it arises because of relatively spontaneous and somewhat re-entrant type activity within the pulmonary veins, which are directly attached to the atria.

And caffeine actually – without question – is the compound that influences and has as its molecular target, a molecule that’s very much involved in spontaneous activity in the cardiac myocytes of both the atria and the ventricle. So despite the fact that there’s never been a link in the trials, I’m not sure that they were necessarily selecting the patients appropriately to detect whether or not there is a connection.

Because certainly from first principles and what we know as physiologists and cell biologists, there’s almost a straight line link between caffeine and spontaneous activity. And again, spontaneous activity almost always initiates paroxysmal atrial fibrillation, usually involving the pulmonary veins.

Chris:    And do you think that might go away? Because everybody’s a regular caffeine user, there’s really nobody that saves it up and then uses it just on a race day or something like that. So do you think that once you’re adapted to the caffeine, that you wouldn’t see the same effects?

Peter:    Yeah no there’s no question. Caffeine – you develop a tolerance to caffeine quite quickly and you also lose it quite quickly if you stop drinking caffeine. And now you have the big provider here for caffeine doses is Tim Horton’s and people have speculated for years that they actually spike their coffee with caffeine. But if you take one of their strong cups of coffee after you’ve been weaned off for a week, I would hazard a guess that you would – if you’re prone to spontaneous activity – you’d probably experience a number of the events that are associated with caffeine.

Chris:    Right. And Mark asked another great question which is the connection between acid reflux and a-fib. Can you talk about that?


Peter:    I really can’t because I don’t know very much about it other than the acid…I actually have the condition myself and in fact it sort of triggered me to start to think maybe a little bit more about that because I hadn’t given it very much thought previously. What is interesting though about that is that the vagus nerve runs right along the oesophagus and it’s the vagus nerve that actually certainly is a contributing factor in the development of atrial fibrillation and it’s something that we haven’t talked about yet.

But the slower your heart rate is – the intrinsic heart rate that you have – it’s kind of the more prone many people are to atrial fibrillation and there’s very clear sort of basic electric physiological principles that actually readily explain that connection. And so this acid reflux is interesting to me because, because of this the nerves that actually are the ones that are controlling the heart run right beside the oesophagus.

I mean they run along the oesophagus until they get essentially to the stomach and then they…but they branch out before that and actually intervade the SA node and modify the heart’s beating activity and the electrical properties of the atria are affected by the vagus nerve as well. So it’s a very, very intriguing idea actually.

Chris:    So what causes the acid reflux? Have you had a look at…I’ve heard about connections between small intestinal bacterial overgrowth, some sort of dysbiosis in the upper gut or maybe an H.pylori infection or some other type of dysbiosis. Have you looked into any of the underlying causes of acid reflux?

Peter:    No I haven’t. I have a hiatal hernia so that’s probably what’s causing mine, so I don’t know. And practically speaking, I guess the main thing you could do if you had it is probably reduce your…eat a little bit earlier in the evening, don’t eat just before you go to bed because it’s going to drive your digestive juices. But no, I actually…when Mark mentioned this to me, I really had a discussion with 2 of my PhD students to maybe look into the literature a little bit further on this and see whether we can actually come up with maybe a way to look at the relationship.

Chris:    Tell me about proton pump inhibitors.

Peter:    Well I don’t know very much about them. There’s a number of different types and they hit different types of targets. In general, like I was prescribed them for my condition and I actually don’t take them. I elected not to, I told my physician that I wasn’t going to take them because I think there’s fairly…and this is where sometimes a little bit of knowledge is dangerous. I do know that they have been linked to some dementia and I think in some ways – in terms of cell biology – it may be a rationale for that. And the proton pumps are extremely important in a process called autophagy.

And this is something that I guess there’s a Nobel Prize that was awarded – I think 2 or 3 years ago or maybe last year for autophagy. And it’s a process of sort of cellular cleansing. The idea is that you have these organelles, these various structures within the cells that just like the bridge going across the river, buildings, they all wear out after a while and have to be replaced. An autophagy is that replenishing of the organelles within the cells. Well proton…there’s these vessels within cells called lysosomes and other structures that are actually very much engaged in that turnover process, and they require proton pumps.

And so one of the theories behind dementia and Alzheimer’s is that there is a build-up of junk in neuron. And again, I really have no evidence for what I’m saying, it’s just correlative to me. But it’s an interesting correlation, it seems rational that there could be a link between those two. So I elected not to take those compounds and I just try to manage it by sleeping a little bit more upright at night with a couple more pillows and I try not to eat…try to eat early in the evening.

Chris:    I think that’s a great strategy anyway, eating earlier. So if you were trying to entrain a circadian rhythm, then eating earlier in the day while it’s still light out rather than late at night right before you go to bed may be an optimal trustee for that reason.

Peter:    Yeah I think so, that’s how I decided to try it – try to manage my condition.

Chris:    Mark had one other point about vagal nerve activity and heart rate variability. So you can measure – perhaps you can measure parasympathetic activity using heart rate variability and I certainly know from my own data that once I’ve been riding my bike a lot for several days, I see very strong parasympathetic activity and that may lead to a lower heart rate. And that seems to be related to the risk –as you said earlier – of premature contraction. So I almost think of this like a runner on the starting blocks and the longer that you keep them in that holding position where the gun hasn’t quite gone off, the more likely they are to spring out the blocks too early and that may not be a good thing for your heart. So do you think it’s a good idea to track heart rate variability and then maybe back off once you see – or before you see – this huge increase in parasympathetic activity?


Peter:    I’m absolutely amazed at your insight and the way you broke down the relationship between spontaneous activity as I tried to articulate it and the slowing of heart rate. Because that’s exactly how we think about it and we use the term increasing the vulnerability period. If you slow the heart rate, you’re just more likely to get some random event from [00:56:09] [indiscernible] from the pulmonary veins. Now as far as should you try to minimize the parasympathetic activity and the heart rate variability, the heart rate variability actually is indeed primarily driven by the vagus nerve.

And actually the variability comes primarily minute to minute, second to second from the interaction between your breathing and your heart’s activity. And the reason is because every time you inspire, you actually create a little bit of negative pressure in the chest which is where the heart is. You pull more blood towards the heart and then that result is that the heart has suddenly more blood at its back end and it will spontaneously therefore increase the amount of pumping that it actually does. So in response to your breathing, your blood pressure actually goes up and down and this vagus nerve is linked to your brain – as I already mentioned – and it’s controlled through reflex called the baroreceptor reflex.

And that’s really what’s causing this heart rate variability and what we mean by that is that it’s a second to second change in the time between beats of the heart. So I think with that background, if you have a stronger vagus, the primary impact of this - I mean having an increased heart rate variability is now going to be inevitable because you have more vagal activity. But the main danger is just the reduction in your heart rate, the increase in the vulnerability period.

That’s what I would say, at least. And so the variability is just like…it comes along for the ride. It’s not a major factor because it’s the overall mean heart rate that actually is likely to be having the bigger impact through increases in vulnerability. And the other thing that you should be aware of – and I did mention this already – and that is the vagus nerve actually releases [00:58:15] [indiscernible] but it releases a substance that actually changes the intrinsic electrical properties of the atria as well. And that also – and I mentioned this before – from first principles in electrophysiology would make you more susceptible to any kind of re-entry sort of event like those that you might see in atrial fibrillation. So it’s sort of one of the factors that actually promotes atrial fibrillation, large amount of vagal activity.

Chris:    Okay. I guess the HRV thing was somewhat of a red herring then, I could just measure my pulse even with my fingers and a clock first thing in the morning. And once I see I get to that stage where there’s a greatly reduced heart rate, then maybe that would be a good time to back off from exercise perhaps.

Peter:    Yeah you know it’s one of those things that goes along with exercise so I’m not sure that you can ever really [00:59:11] [indiscernible]. As you become more fit – the more fit you are is the more vagal activity you put out. So that goes hand in hand, it’s hard to separate those two I would say. Now having said that, there are drug companies now that are trying to develop agents that are specific to the atria that actually block the impact of the factors of the vagus nerve releases and actually block those at the level of the atria and maybe at the level of the SA node

Chris:    Okay interesting.

Peter:    So it’s one of the strategies that’s actually being looked at for preventing and maybe treating bouts of atrial fibrillation.

Chris:    Okay I have one final question for you which is do you think the ablation procedure is over-performed? So we’ve talked about some of the potential underlying root causes – alcohol being one, tumour necrosis alpha, perhaps caffeine. I’m sure there’s other things that can contribute and my concern is the ablation procedure is being performed without really understanding the underlying root causes. So you’re basically putting a great big Band-Aid onto this problem when really what you want to do is adjust the underlying root causes which may involve some diet and lifestyle changes for the athletes. So do you think that’s true? Do you think the ablation procedure is over-performed?


Peter:    Well I think that if you’re a person that has frequent paroxysmal AF, you’re eventually going to – almost always – go on to develop chronic AF. And I would say that the consequences of that can be devastating because something we haven’t talked about yet is that one of the main side effects of atrial fibrillation – besides the fatigue and the inability to perform sport, which is devastating for an athlete. Less devastating for a person that has heart disease. The other real issue becomes that of increased incidents of stroke. And so I would say that coming back to – so I can answer your question in 2 ways. First of all, I think ablation is a godsend for individuals that are at the stage that I was at, where you have paroxysmal AF and you’re going to go on to permanent AF.

    And the reason is because it is a Band-Aid but it does prevent those events that prevent the fatigue and they also prevent even more importantly the strokes from actually occurring. I mean you have about a ten-fold or so – might be a little high – but a large increase in the likelihood of developing a stroke, which obviously is devastating. So it is a Band-Aid. And the problem is that we really don’t know what the factors are. We know that aging is associated, we know endurance exercise, we know on the other end of the spectrum heart disease is associated with it.

We don’t really have a unifying principles upon which we can really build and begin to make recommendations in terms of lifestyle changes, maybe drugs for prevention. We don’t have that. That’s exactly our approach in our research; we’re trying to get at what we think are the fundamental events. And I’m just going to…if this is the last question, I’ll just end on this. We believe that – and I mentioned this already – that the TNF alpha is a mechanal sensor. It’s sensing the stretch. What’s interesting about endurance exercise is that what happens every time you exercise is exactly the same thing that an obese person experiences, another person with cardiovascular risk factors experiences.

And that is those individuals almost invariably also have high back pressures or high pressures on the back side of the heart. So we believe that we’ve latched onto – or lucked out and found – a mechanism that’s probably applicable to both kinds of factors that actually are contributing to AF. And one of our big areas of research now is we’ve developed some – we’re developing actually I should say, because we haven’t gotten there yet. We’re developing models of heart disease where we’re actually doing what we call volume overload.

So we’re actually just trying to specifically backload the back of the heart – load up the hemodynamic through the back of the heart. And again, this happens in many, many different kinds of heart disease, and to see whether or not we get the same kinds of changes and whether or not TNF alpha’s also involved in that form of remodelling. We would use other models of frank heart disease but we already know that the rodent studies have shown that TNF alpha’s very much involved in many of these other conditions. So we want to just get a much purer sort of intervention that just backloads the heart and we believe we’re going to try to backload the heart exactly the same way that it happens in exercise.

Chris:    Wow, that’s amazing.

Peter:    Yeah this is exactly how we’re thinking about the problem and the reason is really directly related to your question. The bottom line is everything that we know right now is all Band-Aid. Once you’ve got the electric disturbance, we can break the electrical disturbance. But the problem is when ablation can do that, drugs can do that to some extent – the problem is the atria are still remodelled. They’re still adversely affected by whatever condition you have that has led to it. And again, aging is one of those. And until we have those insights, we’re probably not going to make very much progress is how I feel. And so that’s the approach we’ve taken, is to try to get at fundamental factors that might [01:04:54] [indiscernible] these changes.

Chris:    How can people find out more and support your research?

Peter:    We’re actually doing some of our research through The Heart and Stroke Richard Lewar Centre at the University of Toronto and the University Health Network – Toronto General Research Institute. Most of our money actually comes from the Canadian Federal Funding agencies. The Heart and Stroke Richard Lewar Centre is actually a centre that accepts donations. They support a lot of pilot projects in a variety of different areas, and we’re actually initiating and trying to set up a specific centre right now at the University of Toronto combined with York University in order to look at this in a very holistic way.


Peter:    So to have some animal models and to try to translate this into – in this particular case – human athletes. And we’ve actually got an ongoing study where we’re looking at cyclists and we’re doing MRIs. We’re tracking magnetic resonance imaging, getting high quality images on these athletes and then trying to track them for a long period of time. And so we’re trying to build this centre through the Heart and Stroke Richard Lewar Centre to really take this from the bench all the way to the athlete.

Chris:    That’s amazing. Is there anywhere else that people should go to, to find out more about your work or learn more about some of the things you’ve been talking about today?

Peter:    Well you could probably check my websites out, you’ll see that I’m at York University as well as at University Health Network, Toronto General Research Institute. And then if you do a PubMed search, you can…

Chris:    Select the author, yeah. So I will link to all these things in the show notes for this episode and I’ll link to the advanced PubMed search so that people can find your publications easily. Peter, this has been absolutely amazing. You’re amazing and I’m very grateful to Mark Federman for the introduction. I hope that we can connect again in the future ‘because I feel like you’re just a goldmine of information and I want all of it.

Peter:    Well Chris, thanks very much for the compliments. I have to admit I’m learning on the job. That’s the beauty of being a researcher and in my particular case, I went from having a condition and I just…I went into my lab one day and I told everyone “We’re changing our research. We’re going to begin to shift over to just studying atrial fibrillation.”

And I should just mention one of the other things that we’re doing is developing methods for producing atrial cardiomyocytes from stem cells. And we have a whole project associated with that too and that’s more trying to understand what drugs might be useful. Again translating our most ideas and seeing what impact these different interventions actually have on human tissue without necessarily putting it into somebody’s body.

Chris:    Amazing. Well thank you so much, I really appreciate it.

Peter:    Well thank you, thanks very much for the interview. Yup it was great.

Chris:    Thank you.


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