the not-so-clean library at home. We're in the middle of the COVID-19 pandemic, and I'm thrilled to have with me today a person who has written on this whole topic of Long QT and how to use these drugs, Dr. Michael Ackerman from the Mayo Clinic, who is a triple threat professor, professor of medicine, peds, and pharmacology, but is known to most of us as a genetic cardiologist. So, Mike, welcome to the show. Eric, great to be with you, and thanks for doing this. Well, there's been so much discussion with the use of hydroxychloroquine and azithromycin and what's going on now, and I thought, since you've actually written something on this very quickly, thank you for doing that in an algorithm, what I'd like to do is have you discuss kind of this whole topic of what we're in the midst of. And there's always some people who don't remember some of the basics, so could we start with the basics, for example, just how to measure the QT, I mean, briefly, and the correctional formulas? Yeah, so it's sort of back to the basics, isn't it, Eric? And you'd think maybe we wouldn't need to do this, but both of our good friends, Sammy Viscan published a paper over a decade ago showing that cardiologists in general and even heart rhythm specialists were not that great at confirming the veracity of the computer-derived QTC calculations. So it is back to the basic, but it's actually really, really easy. LEAD-2 and LEAD-V5 is the rhythm lead of choice for confirming the computer's QTC. We do the Arthur Wildean teach the tangent approach and go down the downslope of the T-wave and intersect it at the isoelectric line and then measure that QT interval. And then we heart rate correct it, often with the Bizet's formula, but there's a lot of them. Bizet's, square root, Friederichia, 0.33 exponent, and Framingham and Hodges are probably the four most common, but we rate correct them by looking at the RR interval before that QT, and then we set up certain thresholds. And as you saw in our algorithm, we have green light go, QTC cutoff, we have yellow light pause, and we have red light, please timeout, stop, be careful before you proceed with hydroxychloroquine. And we can do it fast and on the fly. As you know, if you stare at the QT, and that QT is less than half of the preceding RR, we know that the calculated QTC will always be less than 460. So for every patient, which will be the vast majority of patients, we would get the green light go just like that. So it's really not that hard, but we do have to take our time, and we do have to confirm the QTC that the ECG machine gave us, or more importantly now with COVID-19, we may not be using an ECG machine at all, and we may need to be doing it off of the telemetry strip and so forth. So that's what I wanted to get into a little bit. Just, we'll come back to this, but could you just, for those listeners, give us your green light, yellow light, and pause QTC? Yeah, you know, these QT cutoffs that have been used have been sort of all over the place, and it's been proposed that we shouldn't even use these drugs if the QTC is less than 450, suggesting that that's a high end of normal, and that's just completely wrong because those values are values derived in healthy people. And we previously did a study here at Mayo Clinic, and showed that what are the 99th percentile values in healthy people, which is under 460 before puberty, under 470 in men, and under 480 in women, those aren't gonna be the 99th percentile values of the QTC in people who are coming for medical attention for whatever reason. So they actually turn out to be about the 90th percentile values. And so that's why we set that as green light go, that in that subset, who are less than 460 before armpit hair, less than 470 men, and less than 480 women, there should be a lot of therapeutic margin, therapeutic window, should be plenty sufficient to handle hydroxychloroquine and azithromycin. And if you're above those, but below 500, you get the yellow light. And if you're at or above 500, even before you see these drugs, we better give you the red light stop, and we might treat you, but we better do a lot of other things before somebody should put that person, which is the one percenter of that person on hydroxy. So Mike, that's fantastic. I read your paper, and I like the eyeball test. That seemed really good, unless, of course, someone's rate's 30. You may fail on that one. But I think that's a great quickie. A lot of discussion also that I've been reading in the last four or five days, well, what do you do if it's a bundle branch block? And a lot of our patients may have a pacemaker or a defibrillator. So I've seen a variety of correctional things, and I've read them in the literature, using the JT and so forth. What's your preference if someone has a bundle? Or a pacemaker? Yeah, I like the KISS principle, remember? Keep it simple, silly. Yes. I thought you was a different S at the end. I was a little bit different S, but go ahead. But the way we would do it is, it's hard enough for people to know what the normal QTC value is, and what is the normal QTC cutoff. So if we are gonna now ask them, we want you to remember the JTC normal distributions, I just think it's not gonna work. So what we've done, and what we've built into an online QTC calculator that we're releasing on Monday, is use the standard QTC by whatever formula, and most machines are using Bizette still, and then just do a wide QRS correction. So accept the normal if the QRS is 120 or less. Okay. If the QRS is above 120, whether it's because it's ventricular pacing, or whether it's left or right bundle branch block, or whatever reason, then you just take the QTC, confirm the number, and then you take, subtract the QRS minus 120. So you normalize it as if depolarization was normal to 120, and then you use the same cutoffs, 500, rather than, I've seen it put out there that, if there's right bundle branch block, then you just move the QTC cutoff to 550, and call that your red light. That's why I wanted you to discuss it, because I think that's dangerous. Yeah, I do too, and I don't think, I think it's much cleaner and much simpler just to do a wide QRS adjustment, which you can do kind of on the fly, and we're really excited, this online calculator that will come out real soon. Great. It does it all for you. You just plug in the QT, and you plug in the heart rate, and it'll give you whatever formula is your favorite. It'll read out right away, Bizette's, Fredericia, Framingham, and Hodges for you. So have at it with whatever your pleasure is. I like Bizette still, because that's the one that our ECG laboratory, and our ECG machines, that's the one that the QTC is coming out as, is with the Bizette heart rate corrected formula. Well, that's a great initial discussion, Mike. Let's now go into the heart of things. People are using hydroxychloroquine, plus or minus azithromycin. Nobody really knows effectiveness, so we'll leave that alone. What guidelines would you give us if someone's going to use those drugs, like in your green zone, yellow zone, and red zone? Yeah, the green, yellow, and red sort of presumes you know something called our patient's QTC. Right. And long BC, before corona, we published a paper last summer talking about the QTC as the next vital sign. And Arthur Wilda and I put that forward, Peter Noseworthy and I had put that forward, and we really believe it, it is a vital sign. I really want to know my patient's QTC in many settings, every bit as much as I want to know their height, weight, and their blood pressure on entry to the room. So know your QTC, and that means we have to derive your QTC either by telemetry or by a 12-lead ECG, or by some smartphone-enabled solutions. But the people on the front lines, they probably are saying, sounds good, but I'm not going to be able to get a 12-lead ECG, and I'm certainly not going to have my technician wheel him or herself into the room having exposure risk and PPE use, so that doesn't make sense. So, and I don't have the smartphone-enabled solutions implemented yet, what do I do? The telemetry we can do, hopefully, you can stare at it, and in a split second, see if the QT is less than half of the RR, and you're green light, good to go. But if you can't get the QTC, well then, at least for every patient, we better do a QTC risk factor assessment. Do they or do they not have congenital lung QT syndrome? Well, that's easy, only one in 2,000 patients do. But more importantly, are they or are they not already on a QT-prolonging medication? There's over 100 FDA-approved medications that have a QT-prolonging signal, and when we look at our experience here at Mayo, over 20 to 25% of all patients who had gotten an ECG for whatever reason, they were already on one or more of those medications on the hit list, amiodarone, antidepressants. 10% of the planet are on antidepressants, and those SSRIs are on the QT hit list. So at least, are they already on these drugs? And if so, can we temporarily stop them? Maybe yes, maybe no. And then thirdly, what's their electrolyte health status? We better not add these medicines to somebody whose potassium is already low at three before we then add hydroxychloroquine to the mix and think that we're gonna get away without a perfect storm happening. So you've done your due diligence, and then you decide, based on the algorithm, you go ahead and use them. Talk to me a little about follow-up now. I mean, obviously, you don't know what's gonna happen, and you've done all your precautions like you've suggested. How often does the clinician have to check and remeasure the QT during therapy? Yeah, if we had the smartphone-enabled QT monitor in the patient's room, then we would be able to log the QTC every shift. And see in real time, is our patient showing evidence of declaring themselves as what we call a QT reactor? And I would say it's gonna depend. If you were green light go to begin with, and you have no risk factors, and your electrolytes are good, we may not even need to do a follow-up QTC assessment. If you're yellow light, then we need to. And if you're red light, we said that if you are at QTC of 500 or more before you even got hydroxychloroquine, and for sure if you're gonna get both, because hydroxychloroquine and azithromycin both independently have QT prolonging potential. But if we're gonna treat that red light person, because we've concluded that the benefit outweighs the risk, then we probably should get a on-drug ECG or QT assessment within the first four to six hours to make sure they're not declaring themselves as having imminent torsades around the corner. So I think it's gonna vary. Yeah, I see what you're saying. Mike, let me ask you this. In the great green zone, I like the way you've done it, sounds great. When you start to get into the upper yellow zone or red zone, I'm gonna guess what your answer is gonna be. If a patient is on a drug that's prolonging the QT that's not absolutely necessary at that point in time, I'm guessing you're gonna want them to probably stop that drug. Yes, but again, it will depend. Where are we? Are we in the inpatient setting where we have a- Yes, I'm in an inpatient. I'm shocked I'm in an inpatient. Yeah, so there, if we have the possibility to get ourselves out of a real problem because we did see torsades in living color and now we have to shock the patient, we might have a little bit more appetite to stay on their effective medications that they've been on. But if we're talking, now we're thinking about using these medications in the setting of post-coronavirus exposure prophylactic therapy, which people are already starting to talk about, I don't wanna put that red light person on an outpatient dose of hydroxychloroquine and azithromycin without doing a lot of other things. So I think the setting's gonna depend. Yeah, we can't have our patients on SSRIs, stop their SSRIs cold turkey because that has its own potential consequences. So it'll really depend on what QT prolonging medication are we talking about and do we have room to remove it? And if we can't, we better really make sure the electrolytes are normal. So with every good algorithm, no algorithm is really any good in my own experience unless it's coupled with this. Yeah. It's an algorithm, it's wonderful, but what you're really saying is use some common sense too. Where's the setting? Are there agents they can stop? What's the potential benefit risk ratio for any patient depending on where they are in their disease? And I think that makes a lot of sense, Mike. Yeah, and that's what we did, Eric, with our Mayo Clinic proceedings article, we needed to make sure everybody was well grounded in the risk side of the equation. Right. And we were seeing out there in medical land that the reactions to the use of hydroxychloroquine among cardiologists was ranging still from QT side effect cluelessness, which is why I'm really glad you asked the very first question of back to the basics, to accepting the side effect, knowing that the side effect of drug induced sudden cardiac death is there and just accept it as friendly fire in the battle against coronavirus to total QT paranoia, where they were saying that these drugs are ultra dangerous and they're gonna kill everybody and none of those views are correct. And we needed to give a balance as to what are the risk is. And for you and I to be a good physician or a healthcare provider, the missing piece of the equation is the benefit, because we'll accept a whole lot more risk once we know that these drugs, despite their QT prolonging potential, do in fact have therapeutic benefit against COVID-19. And from my standpoint, that answer isn't there yet as to what exactly is the strength of the benefit signal. Well, Mike, listen, this has been a great discussion. I can't thank you enough for taking out some time to do this. And I know that because I've been working on some things with HRS, I believe your paper is gonna be out for the membership to see at least the algorithm very, very quickly. And if they can jump on this discussion and hear you amplify on these points, it would be wonderful. Thanks so much. And listen, as I like to say, stay in and stay safe, but clearly you're at the Mayo in your office. I'm at my home with my messy library, but I'm hopefully staying safe. Well, I am quarantined in the office. As you see, there's Clorox wipes right in the back. And for all of us, as you know, the best antiviral agent we have right now is to wash our hands with hot soap and water. Coronavirus doesn't like soap. And I'm staying six feet away from everybody. So, physical distancing. Well, stay healthy, Mike. Thank you so much. Eric, take care. Stay healthy. Thank you so much for doing this. Thanks a lot. ♪♪♪

hydroxychloroquine

azithromycin

COVID-19 treatment

QT interval

cardiac arrhythmias