Thank you so much, Dr. Bennett. Congratulations on the Bengals' victory today. That picture of me was actually taken just before the pandemic, which is crazy, because you can see all my hair color changed after that. But thanks for coming today. I was given the title Upstairs, Downstairs, New Onset Atrial Fibrillation Comparing Therapeutic Treatment Strategies Between the ICU and the Emergency Department. All right, let's see if we can move the slides forward. What's that? There's nothing on here. I just have a mouse. Yeah, roll it. Yeah, that's what I'm doing. No. Sorry, just got to figure out how to move the slides. All right. There is more than one slide. I hope. I hope. Oh, here. Oh, it's on the pointer, not the mouse. All right, my only disclosure. Thank you very much. No, thank you. So it's a good thing that we have one of the talks didn't come, so this extra time won't put us over. I have some funding from the NIH to look at atrial fibrillation in sepsis, is my only disclosure. So the assignment for this talk was about addressing the different underlying causes and treatment options for the ICU compared to the emergency department for patients that present with atrial fibrillation. But I am someone who likes to simplify things and think about overarching themes. So surprise, those approaches are very similar. So we're going to try a more unified approach to atrial fibrillation in the ED and the ICU and try to think about one approach to atrial fibrillation. So in this approach we're going to discuss, we're going to ask three questions. I don't think these three questions will be surprising to any of us. Is atrial fibrillation causing the immediate problem for our patient? Why is atrial fibrillation happening now? And should I worry about the longer-term problems that might be related to atrial fibrillation? Because I am a medical ICU doctor, most of the atrial fibrillation I see is what I'm calling secondary atrial fibrillation. So that's AF that is occurring secondary to another problem that brought the patient into the ICU. They're not coming to my ICU usually because of only atrial fibrillation. So we're going to start with a case. This is a case that I saw that brought up a lot of questions for myself as I was going through my career in terms of research. A lot of the patients that I see I'm not sure what to do with and brings up great research questions. So for sort of the trainees in the audience, the patients you see bring up questions that can then lead to research careers. This particular patient was a 62-year-old woman. She has a past history of obesity, hypertension, diabetes She came to our emergency department with abdominal pain. She was slightly hypertensive on arrival, had diffuse abdominal tenderness and a normal abdominal CAT scan and was admitted to the medical floor. She quickly developed chest discomfort and a heart rate right up to the 160s with irregular rate and rhythm and her telemetry showed atrial fibrillation with a rapid ventricular response. Her blood pressure had come down during this time. So initially her clinicians that were taking care of her. So going back to our questions, in this patient is the atrial fibrillation causing an immediate problem for our patient? And so I'm going to say yes, right? The patient has a heart rate higher than what it would be if she was just acutely ill and she has a drop in blood pressure and she has new symptoms. So we're concerned about this patient overall. What's going on with her? But also this atrial fibrillation seems to be doing something bad to our patient and we need to address it. So my thought is if the atrial fibrillation is causing a problem we need to do something quickly. So the two things that we can do quickly are to try to stop the atrial fibrillation which we call rhythm control. So there's a telemetry strip that's converted to not normal sinus rhythm or we can try to slow down the heart rate which we call rate control. So we have patients, they're still in atrial fibrillation, but their heart rate is in a more acceptable range to meet our hemodynamic goals. So when should we think about rate control first? So our ACLS algorithms tell us to think about rhythm control first, think about rhythm control first, when a patient severely decompensates due to the atrial fibrillation, they have new shock, new heart failure, new altered mental status, cardiac ischemia, any sign of end organ damage that we think the atrial fibrillation and the decreased cardiac output that it's causing is perpetuating. So if we think that's happening, our ACLS guidelines tell us to pursue direct current cardioversion and that is often the right approach. For patients coming into our ICU, if we are choosing immediate cardioversion for these patients, we want to also think about pairing it with an antiarrhythmic such as amiodarone to increase the probability that that cardioversion sticks, right, that the patient doesn't go back immediately into our atrial fibrillation and we enter an endless cycle of cardioversion, which is not fun for anyone. However, in non-emergent atrial fibrillation, we still can think about immediate cardioversion or a medical rhythm control strategy using medication first, if we think the patient needs their atrial kick, so a patient that needs atrial systole because they have atrial mitral stenosis or severe aortic stenosis, or if we think the patient can't control a nodal blocker because they have an accessory pathway, for example, a patient with Wolff-Parkinson-White syndrome. There are caveats to jumping in always with a rhythm control strategy first, and really the biggest caveat I think is the risk of arterial thromboembolism, which is increased especially right after cardioversion. So the time after cardioversion is a time of risk for thromboembolism. And although we are taught that that risk of thromboembolism is negligible, if someone has atrial fibrillation for less than 48 hours, the data doesn't truly bear that out. So in this study from JAMA from 2014, from a finished registry study where they looked at patients who were cardioverted for atrial fibrillation that was documented to be less than 48 hours in duration and therefore did not receive anticoagulants. There was a substantial or clinically significant risk of stroke, especially so even for patients that had atrial fibrillation lasting just 12 to 24 hours, there was about a 2% risk of stroke within 30 days after cardioversion without anticoagulation. So we want to think about anticoagulation actually in everyone that we're going to cardiovert. In this study, patients that, like our patient who presented with the belly pain, 10% risk if they had both diabetes and history of heart failure. That's even for atrial fibrillation lasting less than 48 hours. So we talked a little bit about rhythm control strategies, but when to consider a rate control strategy. For me in the medical ICU, a heart rate control strategy is generally what I consider first. So my opinion is that in most instances you can think of a rate control strategy first. When would you think about a heart rate control strategy? Well, if the patient has a heart rate that's higher than it would be, if they didn't have atrial fibrillation and had acute illness, then that's when I generally start to think about trying to lower their heart rate. So some patients have atrial fibrillation and they're critically ill and we don't think the atrial fibrillation is causing a problem. Their heart rate is in the 80s or 90s and that's what it would have been if they were sick with their pneumonia anyways. You don't necessarily have to go and treat that atrial fibrillation, but if we think it's causing harm, we want to treat it. Okay, and then another time to think about a rate control strategy is if the patient has contraindications to anticoagulation because, like I said, the risk of stroke is much higher if you cardiovert them than if you rate control them, at least in the short term, which is one of the things we're worried about for me in the ICU. So what is the evidence to support a heart rate control first strategy during secondary atrial fibrillation? That's atrial fibrillation that's happening for patients coming in with an other acute medical illness. Well, first, a rhythm control strategy with cardioversion doesn't work well for very long for acutely ill patients. So in this study by Erigo, where they looked at the success rates of electrical cardioversion for critically ill patients, only 43% of them remained in normal sinus rhythm at one hour after their electrical cardioversion, and only 23% remained in normal sinus rhythm after 24 hours who were cardioverted for their atrial fibrillation while critically ill with something else. Thinking about medical rate control versus medical rhythm control strategies, in this randomized trial that took place in the emergency room by Sue et al. that was published in Critical Care Medicine, they randomized 150 patients to receive either amiodarone first, digoxin first, or diltiazem first. And their primary outcome was heart rate control. And this is a study that was published in the New York Times. Their primary outcome was heart rate control, and this is on the x-axis the number of hours after enrollment and the y-axis their heart rate. And as you can see, diltiazem resulted in better heart rate control than either amiodarone or digoxin, at least for up to about 24 hours. So these two pieces of evidence, I think, argue that a heart rate control strategy first is reasonable. So in that randomized trial, we saw that calcium channel blockers resulted in a better heart rate control than amiodarone or digoxin. But what do people do out there in the world in their practice? So what do all of you do if we were to survey you? We did a study looking at this. So we looked at about 40,000 patients hospitalized with sepsis who also had atrial fibrillation. This was in a large database that about 20% of hospitals in the U.S. And what we found was that calcium channel blockers were indeed the most common first choice for an intravenously administered medication to treat atrial fibrillation during sepsis, followed closely by beta blockers, and then digoxin and amiodarone were lower down on the list of choices. We then leveraged this variation in practice around prescribing rate and rhythm control medications for atrial fibrillation during sepsis to look at what drug was associated with better outcomes. So we compared beta blockers to calcium channel blockers and then also to digoxin and amiodarone. I'm going to have you focus more on the beta blocker versus calcium channel blocker comparison because that has more equipoise and probably less prone to confounding than reasons why people might choose digoxin or amiodarone over beta blockers for sick patients with sepsis. But I was surprised to see that among all patients and then among multiple subgroups, patients who received a beta blocker actually had a slightly lower mortality risk than those who received a calcium channel blocker for management of their atrial fibrillation during sepsis. So beta blockers might be a reasonable first choice for atrial fibrillation amongst our critically ill patients. Here's some more evidence to support that. Nick Bosch, who is an early career faculty at Boston University, looked at, in a single center, patients who received, who were critically ill with sepsis and who received either beta blockers, amiodarone, calcium channel blockers, or digoxin as their initial drug during their ICU stay with sepsis, and found that within one hour, beta blockers resulted in the highest percent change in heart rate, a 15% change. That was significantly higher than the other three medications. But the improved rate control, or improved heart rate response of beta blockers vanished by six hours. Similarly, if we just look at the average heart rate, patients with beta blockers had lower heart rates at one hour than those treated with the other three medications. Again, that lower heart rate, the significant difference has disappeared by six hours. So taking all this evidence together, when we adjusted for baseline heart rates, multiple clinical confounders, it appeared that beta blockers gave the best rate control as an initial choice for atrial fibrillation during sepsis. So the other question that we wanted to ask ourselves for patients that had acute onset of atrial fibrillation in the ICU setting, or the emergency room setting, is why is the atrial fibrillation happening now? And so this was supposed to be, I think, the subject of the first talk. And while I don't want to go into the details of this complicated figure that asks the question, why is the atrial fibrillation happening now, the take home of this figure is that the reasons for atrial fibrillation happening now are myriad and involve both pre-critical illness factors and intracritical illness factors, and also provide multiple areas for us to intervene. The primary things that are associated with development of new onset atrial fibrillation during acute critical illness, at least in the medical ICU as I see it, are electrolyte problems, so potassium and magnesium issues. Magnesium infusion is actually a rhythm control strategy, and compared with amiodarone, initial use of magnesium in a small study was associated with similar rates of conversion. So giving magnesium is an additional strategy for atrial fibrillation during critical illness. Problems with volume status can trigger atrial fibrillation, both hyper and hypovolemia. A big one in our ICU is untreated infection and sepsis, and sepsis is a very strong risk factor for atrial fibrillation, actually compared to other reasons for hospitalization, sepsis is associated with a seven-fold increased risk of atrial fibrillation. And lastly, this beta agonist we give to our critically ill patients can trigger atrial fibrillation, and removing those beta agonists is another approach. So fixing things we can fix, there's not a ton when it comes to atrial fibrillation, but there are some. So let's talk a little bit more about decreasing beta agonism for our critically ill patients and how that relates to atrial fibrillation. So one of our other early career faculty at Boston University, Anika Law, addressed this question of what happens if you reduce the beta agonism of our patients who are going to start vasopressors in our ICU who have atrial fibrillation. So what she looked at was in the blue line here, patients who started phenylephrine for shock, and in the red line, patients who started norepinephrine for shock, with the obvious difference that norepinephrine has beta agonism that phenylephrine does not. Thank you. And so time 0 here is the time they started the vasopressor, and time negative here is the hours of their heart rate before starting, and positive time is the hours after starting. And as you can see, in just these crude plots of heart rate pre-post-starting, the vasopressor patients who started phenylephrine had lower blood pressures, both in the full cohort, in those that had a rapid ventricular response, and less so in those that did not have a rapid ventricular response to their atrial fibrillation. In our multivariable adjusted models, at six hours, those patients who had started phenylephrine instead of norepinephrine had about a six beats per minute on average lower heart rate. So less beta agonism associated with less tachycardia, sort of something that you might think is obvious, but hasn't really been shown when thinking about the starting of vasopressors for patients with atrial fibrillation. So how might we think about new atrial fibrillation in the emergency department or ICU? So our patient has new atrial fibrillation, like the one that we saw coming in with belly pain. We want to ask, is it causing hemodynamic compromise? And if we think the atrial fibrillation alone is causing severe hemodynamic compromise, we will do ACLS pathways and cardiovert them. However, I will argue that's actually fairly rare. And the atrial fibrillation that accompanies critical illness often exacerbates an underlying problem but doesn't often itself result in severe acute decompensation, but needs to be addressed. We want to think about our offending agents present. That can be beta agonists, that can be other antiarrhythmics, that can be vasopressors, that can be electrolytes. There's reversible factors, ventus synchrony, myocardioschemia, volume status like we discussed. Are we missing something? That's a major question we want to think about with nuanced atrial fibrillation. Patient's gotten worse, why? And then, if despite addressing all those underlying issues, the atrial fibrillation is still present, we want to ask, are the adverse effects of atrial fibrillation due primarily to an elevated heart rate? Or are the adverse effects due primarily to loss of atrial systole? If we think it's just the heart rate, then a rate control strategy first I think is reasonable. In our ICU we often choose Esmolol as the initial treatment of atrial fibrillation for patients who are critically ill who develop new atrial fibrillation with rapid ventricular response, mostly because Esmolol, if you've chosen poorly, can be turned off and has a half-life of about one minute. So if you make a mistake, the mistake won't haunt you for a long time. If you think that the patient needs to be in sinus rhythm, then we often will give a magnesium infusion and then start amiodarone if that didn't work. So what we haven't talked about really is what about the risk of arterial thromboembolism. So arterial thromboembolism is a known complication of atrial fibrillation, generally resulting from stasis of blood in the fibrillating atrium that causes it to clot and get thrown most concerningly to the brain. Arterial thromboembolism and AF recurrence are generally longer-term concerns after new atrial fibrillation in a critically ill patient. For example, in one of our studies following up patients after they had new onset atrial fibrillation in the ICU, 44% had an atrial fibrillation recurrence within the year after their critical illness. It's fairly common for patients to have recurrence of their atrial fibrillation that they first had in the ICU. It's not something that if you treat the critical illness and it goes away that you can trust that it's gone away for a long time. However, also in one of our studies where we looked at patients with sepsis who are treated with anticoagulants, using anticoagulants during the acute phase of sepsis for new onset atrial fibrillation was not associated with lower stroke risks but was associated with higher bleeding risks. So our practice is to keep an eye on the patients and as their critical illness resolves then to start to think about shared decision-making about longer-term anticoagulation. And that's because if you look at this figure here where we followed patients for five years after their hospitalization with sepsis, you can see that in the green line here, that's patients that did not have any atrial fibrillation during sepsis. In the blue line, patients with pre-existing atrial fibrillation. And in the red line, those with new onset atrial fibrillation during sepsis who have a stroke risk that sits in between the two. So they have a significantly higher stroke risk over five years as compared with patients that did not have atrial fibrillation during sepsis but lower than those with known AF. So the anticoagulation questions for patients with new onset atrial fibrillation are a little more complicated just because the risk-benefit scale for patients is not the same as for patients with known prior AF. So back to our patient. This patient was started on intermittent diltiazem pushes to get the heart rate down to the 120s, admitted to the hospital ward from the emergency room. Then the heart rate was unable to be controlled and the patient was admitted to our ICU for a diltiazem infusion where we met her. After a brief improvement on the diltiazem infusion that was started on the floor before she was transferred to the ICU, she suddenly became hypotensive and more short of breath. A test was ordered to evaluate her shortness of breath and she now had free air under the diaphragm. So she was sent to the OR to repair bowel perforation, which brings up our last take-home message that new onset atrial fibrillation secondary to a medical illness means that something is wrong, okay. Something that you might be missing. So Jake Bosch, who we discussed before, did this study that showed that atrial fibrillation in patients with a new infection acts the same as any other sepsis-defining organ dysfunction in terms of mortality risk. So atrial fibrillation, that's new onset, has a similar mortality risk for someone with an infection as new renal failure, new vasopressor requirement, new respiratory failure. So atrial fibrillation, we think, is actually a sepsis-defining organ dysfunction that represents cardiac dysfunction, which means we need to address the underlying cause of why the atrial fibrillation happened while simultaneously seeking to control heart rate and heart rhythm. So in summary, rate control for new onset secondary atrial fibrillation is usually sufficient to achieve hemodynamic goals while addressing the underlying cause, at least in our medical ICU. Rhythm control may be needed in emergent situations where the atrial fibrillation we believe is causing itself the severe compromise, or if rate control fails, but may trigger stroke and may require anticoagulation. Anticoagulation decisions to prevent long-term arterial thromboembolism risk can generally be made after the acute illness is resolving because the risk for stroke in the short-term is low. And that means that post-hospitalization follow-up is needed for patients with new onset atrial fibrillation during critical illness. And that's probably the most critical part to get them follow-up for rhythm control monitoring and further treatment decisions. Thank you very much.

atrial fibrillation

emergency department

rate control

rhythm control

beta blockers

follow-up care