Dr. Tselios is an Assistant Professor of Medicine with the Division of Rheumatology at McMaster University since 2021. He completed his basic training and PhD in Greece and came to Canada in 2014 where he worked as a post-doc fellow with the University of Toronto Lupus Clinic. His main clinical and research interest is the field of autoimmunity and systemic lupus erythematosus, particularly the cardiovascular complications of the disease. He has published more than 70 peer-reviewed articles and book chapters. He is currently developing the McMaster Lupus Clinic and Lupus Ontario/Anne Matheson Lupus Biobank in Hamilton.
Time Stamps in minutes of our conversation:
2:00 I started looking after lupus patients in 2008 in Greece, and was offered an opportunity to do a PhD in lupus to become the medical director the lupus clinic …and there, I fell in love with lupus patients and the process of the lupus disease.
4:21 My published research caught the attention of the Toronto Lupus Clinic run by doctors Touma and Gladman
who were collecting data on lupus patients since 1971. This clinic at the Toronto Western Hospital at the University Health Network is one of the largest lupus clinic in the world, was a great environment for me to gain expertise in lupus. I worked there since 2014 and it was a great experience.
5:00 I stayed there for 6 years as a post doc. Then I was hired at McMaster University in the Division of Rheumatology at Hamilton Health Sciences. My main goal is to develop a new Lupus Clinic for south western Ontario and this Biobank, if we want to talk about it further is about collecting samples for further lupus research.
6:00 Heart involvement and lupus: In the past lupus has been so agressive that it leads to often leads to death. But most people do significantly better now. So our patients will survive but the arteries can stiffen as the years go by (atherosclerosis) and as we get older.
8:00 Lupus patients are 50% more likely to have a heart attack than people without lupus. This is huge. I was trying to understand, what is happening with the heart in general with lupus patients and why lupus patients get more heart disease and more severe heart disease.
8:22 I started investigating this in my research with the Toronto Lupus Clinic cohort. As you dig deeper into research sometimes you find things that you would never expect.
8:60 The heart conduction system is about the heart pumping blood to every part of the body: the skin, the muscles, the organs.
9:36 There is a neural network through the body that controls the heart rate rate. We call this neural network that controls the heart rate, whether that are is 60, 70, 80 or 30.. we call this the heart conduction system of the heart. We have identified 2 nodes for this the sinus node and the AV atrial ventricular nodes for this in the heart. All the nerves that connect one node to the other give the muscle contraction of the heart to work as a pump.
10:14 This is the conduction system of the heart and it is autonomous. You can’t control it. You can’t stop your heart rate. Your conduction system is there to do the work for you.
11:14 This neural network is electrical. This is what the EKG shows. So thisis what we are looking into, the conduction system and if it is working properly.
11:30 In our 2018 Research paper “Severe brady-arrythmias is systemic lupus erythematosus: prevalence, etiology, and associated factors “
12:51 I will explain what brady- arrhythmia is and why we did the research and wrote the paper. Whatever heart beat is irregular we call it arrhythmia. It is a Greek word that means irregular rhythm. Brady is also a Greek word that means slow. So a brady arrhythmia is a really really slow heart beat. The word severe indicates that these are the cases that need a permanent pacemaker in order to support the heart function.
13:14 In these cases the conduction system is failing and in order to prevent complications like sudden death we go with a permanent pacemaker.
13:33 The motivation for this paper, was a patient I had who was in her 70s. She had lupus since her 20s. She was fine for 15 years and all of sudden she developed heart failure.
14:10 After 6 months we still could not figure out why that happened to her. So we did a heart biopsy – we take a little piece of the heart and check it under the microscope. We are very lucky in Canada to have this advanced medicine. But what happened? The patient was taking hydroxychloroquine (plaquenil). Plaquenil is prescribed almost universally in lupus patients.
15:22 So this heart condition of my patient had been caused by prolonged plaquenil treatment. She had been taking it for 13 or 14 years at the time.
15:37 We stopped the Plaquenil. And it took months. Plaqenil goes into the muscle and heart fibres and it can months and years for it to go away.
15:57 After that I thought I have 1300 to 1400 patients on plaquenil.
15:57 After that I thought I have 1300 to 1400 patients in the Toronto Lupus Clinic on plaquenil. I had to find a way to see what was happening with the other patients. But it was impossible to think about biopsying this many patients. It very expensive, invasive and dangerous to do. So I went to the literature and I found all the cases from 1967 to 2016 to see what was happening.
17:12 I found 47 patients from around the world with heart problems and more than half had received a permanent pace maker.
17:47 A permanent pacemaker means that these patients had an arrhythmia severe enough to threaten their lives. Otherwise they would not get a pacemaker. I thought ok something is happening here.
18:24 It is likely that the Plaquenil is causing heart conduction problems. So I went to the goldmine of the database of the Toronto Lupus Clinic with Dr Murray Yurowitz
Since 2001 Dr Yurowitz documented since 2001 to 2017 if and when lupus patients had a pacemaker. I went back to the original charts to see what their EKG was before the pacemaker and what the indication was for the pacemaker. I was reading hand written notes in individual patient records. I put all this information together in a table.
20:48 I had a control group of patients who were the same age. And I wanted to know what made the pacemaker patients different than the control group of lupus patients who were the same age, same gender, same but had no pacemaker requirement. I tried to do the work in a methodically sound way so that my results would be sound.
22:13 We have as we discussed 2 nodes for conduction in the heart the AV and the sinus nodes.. When the signal does not travel to other one this is called a block. The signal is provided by the nerves that connect these two halves of the heart. When there is signal trouble there is nerve damage in the heart.
22:49 When there is no signal in the heart this is called Atrial Ventricular Block (or AV Block). So the heart is pumping blood but it is very weak and it is very slow. You will have a heart rate of 30 instead of 60 or 70 beats per minute.
22:57 The other one is called Sick Sinus Syndrome. The Sinus node in the heart is the location where everything starts in the heart. The sinus node will give the spark for the heart to pump the blood.
23:20 If for some reason that sinus node is sick, as in Sick Sinus Syndrome, you have pauses in the heart pumping ….you may have pauses for 5, 6, 10 seconds…This leads to syncopic attacks, so the heart will stop, the patient will collapse and then be ok again when the heart starts beating again.
23:51 We can test this through Holter monitoring, with a battery pack on your chest that will monitor your heart rate for 48 to 72 hours. Here we will see these pauses and then if confirmed you will get a pacemaker. This is the only choice because you don’t know how long the next heart pause will be.
24:10 So my research showed that lupus patients are 24 times more likely to develop AV block something like this than other people. For sick sinus syndrome it was 4 times higher. When you put this together this is a significant issue for lupus patients.
25:06 And this may even be an underestimation of the situation because both conditions predispose to sudden cardiac death. And in these cases patients will be declared dead but we have no idea what happened because the patient had no EKG, halter monitor or other heart tests.
25:35 On sudden cardiac death, there was a study in Canada, where they were checking on the reason for death in lupus patients and sudden cardiac death was the 4th cause of death. The percentage was 8 to 9 percent – so one out of 10 lupus patients will suffer sudden cardiac death. It is huge.
26:03 The question is, how can we prevent this? The answer is diagnose this early, and intervene and do something to keep these lupus patients alive.
26:27 What I found in my study, when the coronary arteries are blocked in coronary artery disease, the heart gets less blood than it should. If this happens in place A in the heart it only affects the muscle fibres, if this happens in place B in the heart, it will affect the conduction system and the heart beat. This is a well known complication after a heart attack. After a heart attack you may get an irregular heart beat – and you can get a pacemaker.
28:44 And then I found patients who have had heart surgery, so it is likely that you will get some damage from the surgery and then you will get a pacemaker.
28:54 For 8 patients in my study everything was good with them, they did have CAD, surgery, but all had eye disease from plaquenil.
29:00 Eye disease is a well known complication of plaquenil. Lupus patients are sent to ophthalmologists every year to get a special field of vision test because we know that plaquenil goes to the back of the eye, the retina to deposit cells called melanin and will cause damage.
30:20 These patients had eye disease and arrhythmias at the same time. So the drug likely does not only go to the eyes but it goes to the heart.
30:37 In the sixties they were giving similar drugs to dogs in experiments, I am sorry to say we were doing horrible experiments on animals in the pat before the ethics committee started to put everything in order. So they were given this drug to dogs in hopes that they would find signs of toxicity. What happened with this is that the dogs that had high doses of this drug Plaquenil had heart problems exactly where the nerve systems of the heart lie. So the drug was being deposited in the nerve conduction part of the heart and disrupting heart conduction. We don’t have similar studies in humans but we haven’t checked yet.
31:52 The other thing that I found, is that plaquenil goes to cells that have something called melanin. We have these in the skin – and some of us are darker than others — so have more melanocytes under the skin. We have people who take plaquenil for many, many years and their skin gets darker because of this.
32:46 So what’s happening in the heart? I checked the literature and to my surprise I found that some melanocytes were found around the heart around the heart valves. So the drug will go exactly to these cells, be deposited there, and is now causing trouble. What they are doing there we have no idea. We know that these melanocytes contain a protein, but we don’t know what other properties they have. There are some studies that connect them with the conduction of the heart.
33:50 In any case after patients have taken plaquenil for many many years… these patients were taking plaquenil for 22 years on average…may give some heart trouble and irregular heart beat.
*here Verla gives her story of following her resting heart rate and heart rate variability, taking this info to her physician, who ordered a holter monitor for 72 hours. Together they decreased her plaquenil to 200 mg. *
35:22 This can help patients because what I found in the heart ultrasounds of the patients (35:29) that there are EKG findings that you will see that predispose you to this arrythmia – this irregular heart beat.
35:44 It is called RBB (Right Bundle Branch Block) – about half of the patients who had heart conduction problems have this. Another block called LAFB.
36:21 Now what is happening with this? If you have RBB you have a high risk of sudden cardiac death. That was from a meta analysis of more than 2000 people with RBB. This increases the risk by 43%.
37:10 If you have either RBB or LAFB you have a 50% chance of getting a pacemaker in the next 5 years.
37:22 We can have this everywhere in Canada, we just have to be alert and aware. We can see if something like this is happening.
37:40 If you have either condition is it reversible? In my experience no. But you can get closer monitoring and have your doctors on the alert for a pacemaker to prevent sudden cardiac death.
38:15 The other thing is that when I checked the hearts off these patients about 60-80% of these patients had a heart that was hypertrophic. This means a bigger than expected heart.
39:11 We have recently confirmed this with heart MRI . In UHN, Toronto Hospital we have a wonderful collaborator, who had heart imaging training in Harvard in Boston who helped us a lot in defining the trouble exactly.
39:46 So this is what we did with this study and what we suggested was this. #1 monitor your patients with EKG and from time to time an echocardiogram.
39:53 If anything like this happens be on the alert that this patient will most likely develop a risk of brady arrhythmia, this low heart rate and will need a pacemaker.
40:11 With regards to the low dosage of the drug, we don’t have the data yet, but in the UK and Canada, we are looking at patients who have low lupus activity or they are in remission, (40:40) decreasing the dosage of plaquenil.
40:44 We want to keep giving plaquenil because it helps with the atherosclerosis, decreasing the number of flares, it helps with survival. And we have multiple studies showing that – so it’s a good drug. It is a great drug for lupus patients, but we have to fine tune its use. It is now perscribed at 5mg per kilo of patient weight and less theoretically are non toxic doses.
42:00 What I am doing for the Lupus Ontario is the largest lupus organization in Canada. They have about 3000 members. About 1000 lupus patients and about 2000 family members and friends. I am working closely with Lupus Ontario. This was the first organization that gave me support for my first fellowship (42:58). So practically they gave me the money to come to Canada. For this I am forever grateful. And that is why we are working so closely and giving webinars, talks, and presentations. We are working together for projects to improve lives for patients with lupus. Anne Matheson was the former president of Lupus Ontario. She is doing well from the lupus perspective, she lives in Hamilton, she is a local hero for the lupus community and we decided to name the biobank after her. That is why it is called the Lupus Ontario Anne Matheson Biobank because Lupus Ontario gave me the money and Anne Matheson devoted her life to lupus.
43:37 What is the biobank? It is a respository of blood samples, DNA samples, urine samples, of patients with lupus. With their consent of course, I will take this blood and separate the serum and the DNA. The serum is the fluid part of the blood without the cells. And I will store this to liquid nitrogen freezer at a temperature of minus 176 degrees. Liquid nitrogen, the samples will be good for future studies for 15 or 20 years. So it will not be modified in any way, there will be no interactions from molecule to molecule …..everything stops at minus 176 degrees. It will be preserved for 15-20 years. So if anyone has a good research idea 5 years from now, and we need to check this, we can go in and get some samples and check it. And splitting this up — I will split the samples up in 5 different ways, we call it aliquots, into 5 different small tubes. So when we check something the tube is destroyed. We can’t put it back in the freezer. But if I want to check something else, another theory, another research question, I will take the second sample.
46:06 I started doing this aliquot samples with genetics, and now am doing with another university in Europe and they are able to do genome/genetic analysis of all my patients on a piece of paper. This is a collaboration and we have many lupus clinics, organizations around the world working together on this.
47:00 Now I have the genetic analysis of my patients, I can follow their disease process, the health of the heart, and put them all together in one database. The ultimate goal is to find out why lupus happens… why kidney disease in lupus happens, why heart disease in lupus happens, why that irregular heart beat happens. If we know why, we can figure out how to prevent this.
48:00 One more thing, I did a study for mortality of lupus patients in 2018
of lupus patients from 1971 to 2013. The coroners office broke the lupus deaths down by decades. From 1971-1980 the mean age of death was 42.4 years.
49:30 Lupus patients at that time were told that they would die after 5 years of being diagnosed. The net decade 1980-1990 the mean age of death was 59.9 so say 60 years of age. The mean life expectancy from 2010 to 2013 for Canadian women was 82 years.
50:43 Still our patients lack 22 years of life. We still have a lot of work to do.
I was looking at this at cause by cause for these deaths. When it comes to infections, we do exactly the same as non-lupus patients. So if a lupus patient gets an infection, we are able to treat as effectively as a non lupus patient. And when it comes to cancer, it is more or less the same. When it comes to heart disease it is 3 or 4 times higher than non lupus patients. So still our patients are dying from heart disease. We have to work better at that, we have to find answers.
We are few in the lupus community but we are strong. I am trying to mobilize resources from the government, from other sources,
Dr. Tselios is an Assistant Professor of Medicine with the Division of Rheumatology at McMaster University since 2021. He completed his basic training and PhD in Greece and came to Canada in 2014 where he worked as a post-doc fellow with the University of Toronto Lupus Clinic. His main clinical and research interest is the field of autoimmunity and systemic lupus erythematosus, particularly the cardiovascular complications of the disease. He has published more than 70 peer-reviewed articles and book chapters. He is currently developing the McMaster Lupus Clinic and Lupus Ontario/Anne Matheson Lupus Biobank in Hamilton.
Time Stamps in minutes of our conversation:
2:00 I started looking after lupus patients in 2008 in Greece, and was offered an opportunity to do a PhD in lupus to become the medical director the lupus clinic …and there, I fell in love with lupus patients and the process of the lupus disease.
My published research caught the attention of the Toronto Lupus Clinic run by doctors Touma and Gladman
