Transcript

PLEASE NOTE: While an effort has been made to correct errors in this AI-generated transcript, some mistakes may have been missed. This transcript should be taken merely as supporting material to the podcast discussion and neither is as an authoritative last word on the subject matter.

MIC CAVAZZINI: Welcome to Pomegranate Case Report. I’m Mic Cavazzini for the Royal Australasian College of Physicians. These Case Report podcasts have been developed to help Trainees work through their long-case presentations, and today’s episode some important differentials for a familiar symptom.

ST elevation is clearly a worrying finding that can herald life-threatening conditions such as myocardial infarction. But not all ST-elevations are created equal, and Trainees would benefit from considering a broader number of causes for this presentation. 

In today’s podcast the team will discuss a case of ST elevation observed in a 65-year-old female during the routine elective procedure of atrial fibrillation ablation. A range of pathophysiologies is discussed that can help listeners work though the differentials in a systematic way.

The case will be guided by Associate Professor Stephen Bacchi who has recently gained his College Fellowship. He’s also just been awarded RACP Trainee of the Year for his diverse contributions to education and research. We’ll put him in the podcast hot seat one of these days to discuss his pet topics, but for now let him guide you through this interesting case. If you want to read along, there’s a link to the report publication in the show notes at racp.edu.au/podcast.  

STEPHEN BACCHI:            Hi, I'm Stephen. I'm a neurology Fellow at the Massachusetts General Hospital, and today we'll be discussing a fascinating case with three guests. Professor Pramesh Kovoor is a cardiologist at Westmead Hospital with an interest in coronary interventions and ablation of cardiac Arrhenius. Dr Neil Warwick is a cardiac anaesthetist at Westmead Hospital with a special interest in anaesthesia for patients undergoing complex percutaneous cardiology interventions in the cardiac catheterization laboratory. And Dr Joshua Kovoor is a surgical service registrar and postdoctoral Fulbright Scholar. Thank you for joining us.

So as usual, we'll be discussing a previously published case report in a step by step manner, with a focus on content that is relevant to trainees and a generalist audience. Josh, could you please take it away with the case?

JOSHUA KOVOOR:           So a 65 year old female received a general anaesthetic for pulmonary vein isolation for atrial fibrillation. This was a repeat pulmonary vein isolation having previously had a pulmonary vein isolation 15 months prior. Otherwise, past medical history included a dual chamber pacemaker for bradycardia and hypertension controlled on perindopril. Her other medication was dabigatran. There was no history of angina. Could you please revisit for us the indications for cardiac ablation, for atrial fibrillation? And who are good candidates for this procedure?

PRAMESH KOVOOR:       The percutaneous procedure of pulmonary vein isolation is appropriate for those patients who are very symptomatic with their atrial fibrillation, and in particular for those patients who have had left ventricular dysfunction,

STEPHEN BACCHI:            And Dr Warwick, what sort of considerations do you have prior to an anaesthetic for these people, who's a good candidate?

NEIL WARWICK:               Anaesthesia could be a challenge with these patients having hypotension, when there are rapid ventricular risks associated with atrial fibrillation, particularly when the presence of left ventricular dysfunction.

STEPHEN BACCHI:            In this instance the patient received midazolam and remifentanil, pre induction, metaraminal infusion missed at five milligrams per hour, and induction was provided with propofol and rocuronium. Dexamethasone, ondensitron and sivafluorine were also provided. A tranoesophageal echocardiogram demonstrated no left atrial thrombus. So Prof Kovoor, why is a transoesophageal echocardiogram performed prior to AF ablations? And in general, what would occur if a left atrial thrombus was visualized?

PRAMESH KOVOOR:       The transoesophageal echocardiogram is performed for two reasons at the beginning of percutaneous pomegranate isolation. The first, and probably the most important one, is to exclude the presence of a left atrial thrombus at the beginning of the procedure. The second is to enable safe transseptile puncture of the interatrial septum to gain percutaneous access to the left atrium for the pulmonary vein isolation procedure. However, nowadays, the presence of left atrial thrombus is very rare. As all pulmonary vein isolation procedures across the world are performed while the patients are on uninterrupted dabigatran or Pradaxa or on warfarin, both of which have reversal agents available. They are generally not performed while they are apixaban/Eliquis or Xarelto because these two agents do not have easily available reversal agents.

If a left atrial is detected at the beginning of the procedure then the procedure has to be cancelled. And then we would need to reconsider our options. If the patient is on dabigatran, and a left atrial thrombus is detected, then then usually we would stop the dabigatran, start the patient on therapeutic warfarin, and reattempt the procedure a few months later, while they are on therapeutic warfarin.

JOSHUA KOVOOR:           So transseptal puncture was performed and unfractionated heparin was used to maintain an activated clotting time, or ACT between 300 and 315 seconds. ST elevation was first noted 35 minutes after induction, predominantly in leads 2, 3 and aVF. Can you please talk us through your differentials for ST elevation in general? i.e. not specifically for this patient, but more in general, for BPT to think about pericarditis, Takotsubo and other conditions.

PRAMESH KOVOOR:       So ST elevation with a convex pattern and which is restricted to particular coronal vascular territory such as anterior wall, inferior wall, or lateral wall, generally, would indicate acute ischaemia. And the most common cause for that would be an acute thrombotic occlusion of a coronary vessel due to a plaque rupture, which is what we would normally call ST elevation myocardial infarction. But rarely, as in this case, it could be due to a coronary artery spasm.

If the patient does not have the standard risk factors for coronary artery disease the other consideration would be Takotsubo cardiomyopathy, which is usually across multiple vascular territories, such as anterior wall, lateral wall, inferior wall, and there would be the convex ST elevation. The other group are the ones with concave ST elevation, which is across multiple vascular territories, such as across anterior wall, inferior wall, lateral wall, which is classically due to acute pericarditis.

JOSHUA KOVOOR:           How about your differentials specifically in this instance? Which factors made them more or less likely?

PRAMESH KOVOOR:       So, in this case, there are a few considerations that went through our mind. The first one was whether they could have been an air embolism, which we might have caused into the left atrium, which could have travelled into one of the coronary vessels. That usually could happen when a new catheter is introduced into the left atrium but in this case, there was no catheter introduction just before this episode, and we were very particular with flushing all sheets and catheters with saline during the procedure, so air embolism was not considered as a possibility in this case.

The second possibility is the presence of left atrial thrombus which embolised into one of the coronary vessels. And again, because we performed a trans oesophageal echocardiogram at the beginning of the procedure and excluded a left atrial thrombus, we did not consider that to be a possibility. Besides, this patient was on uninterrupted dabigotran. And as soon as the transept puncture was performed we gave additional heparin, both as a bolus dose and also continuous infusion straight into the left atrium to maintain ACT around 300 to 350. And in fact, just prior to the ST elevation that was noted, the ACT was about between 340 and 360. So in this case, we considered an acute coronary occlusion as a possibility, which could be either due to plaque rupture and thrombotic Corona occlusion or a coronary artery spasm.

STEPHEN BACCHI:            Well, in this case, the ST elevation was transient, but then it recurred at 75 and 105 minutes after induction, with accompanying hypotension or low blood pressure. After the third episode, coronary angiography was performed, which demonstrated severe coronary vasospasm in the proximal two centimetres of the right coronary artery. There was only minor coronary artery disease elsewhere. So now we know there's coronary vasospasm as the cause of this ST elevation. So Prof Kovoor, the question is, what is the cause? What are some of the common triggers for coronary vasospasm in general and which are most relevant to this patient?

PRAMESH KOVOOR:       Coronary artery vasospasm is quite rare and is one of the disease process that we do not understand very well why it happens. But in this case and the most likely culprit is metaraminol, which is an alpha-1 adrenergic agonist agent. It can cause spasm of the proximal coronary vessel, particularly when there is some coronary artery disease present. Metaraminol, as Dr Warwick would explain, is very commonly used in the anaesthetic world but we see this phenomenon very, very rarely.

And the reason could be that coronary artery spasm with metaraminol could occur in the proximal vessels when there is some coronary artery disease present, as in this case. Without that, it's rare for  it to cause significant proximal coronary artery vasoconstriction. So in this case, the question for us was whether this is an acute thrombotic coronary artery occlusion due to a plaque rupture, or whether it was a coronary artery spasm.

Luckily, because this procedure was performed in a cath lab, on a cath lab table that was capable of performing a coronary angiogram we could undertake the procedure significantly. If the patient was undergoing some other procedure, then that procedure would have been interrupted, the patient would have been transferred to a cath lab to have a coronary angiography.

So to answer your question, in this case, we confirmed that there was proximal right coronary artery spasm, which we demonstrated by reversing the spasm with intracoronary vasodiladilator such as GTN or nitroglycerin, after which we stopped metaraminol infusion that patient was on, started the patient on a continuous intravenous infusion of nitroglycerin. And also to support the blood pressure, we start the patient on noradrenaline.

JOSHUA KOVOOR:           So the procedure was completed successfully, and the patient went home the next day. So Dr Warwick, metaraminol was the most likely culprit here. Could you please remind us of the mechanism of action of metaraminal and how does this differ from noradrenaline?

NEIL WARWICK:               The vasopressor effect of metaraminol is as a pure alpha-1 adrenergic receptor agonist, resulting in peripheral vasoconstriction. It does have the advantage by being a low potency agent of not causing issues if given via a peripheral vein unlike a potent agent such as noradrenaline. It also has a lot of indirect agonist activity. Whereas noradrenaline stimulates both subtypes of alpha receptors, both alpha 1 and 2 and, of course, beta 1 receptors, and it can elicit beta receptor-mediated dilatation of coronary arterioles, thus preventing a receptor mediated coronary vasospasm but typically of the smaller coronary vessels. So, epinephrine, or adrenaline, as it's known here, is an alternative to norepinephrine, which stimulates both subtypes of alpha and beta receptors and induces coronary vasodilation, in addition to elevating blood pressure.

STEPHEN BACCHI:            Well, that was a fascinating case, it would have been very interesting to be there at the time. Thankyou for sharing the case with us, and thank you also to the patient for sharing their story. So, to wrap up the recording, could you please give us some key take home messages that will be appropriate for Trainees?

PRAMESH KOVOOR:       So if there is a STEMI call—as it is commonly known in hospitals when there is acute ST elevation in a patient, and in particular when this happens under general anaesthesia—one of the considerations should be whether the patient is on intravenous metaraminol infusion. And if so, it's important to consider acute coronary vasospasm as a possible cause, and instead of interrupting the operation or procedure and rushing the patient to a cardiac catheterisation laboratory for an urgent coronary angiogram, one possible plan of action could be stop the metaraminol infusion, replace it with a GTN or nitroglycerine infusion, along with an agent such as noradrenaline or adrenaline infusion to maintain blood pressure.

If after this step, the ST elevation resolves, then it would be perfectly appropriate to continue with the procedure or the operation without urgently requiring coronary angiography. However, if the ST elevation persists, then it would be important to interrupt the operation or the procedure, take the patient to a cardiac catheterization laboratory for an urgent coronary angiography.

STEPHEN BACCHI:            And Dr Warrick, are there any principles that you think could be observed in this case, would be relevant for Trainees, particularly physician Trainees.

NEIL WARWICK:               The most important principle is that the anaesthetist is going to be always concerned about, obviously, perfusion pressure and cardiac output. As has been commented, metaraminol is commonly used in order to maintain perfusion pressure, particularly commonly in this subgroup of patients. There is, I think, a general low level of knowledge, even amongst anaesthetists, about the particular problem with metaraminol. Although notably in cardiac surgery, metaraminol administration is always meticulously avoided at the initiation of, say, the beginning of cardioplegia, when often the blood pressure does transiently fall, wanting to make sure that we don't cause any maldistribution of pleasure by possible coronary vasoconstriction.

Whilst that's a specialist area in general, most people are not aware of this particular caveat, but it is something that's important to to remember when metaramanol is used. And so yes, you have to have the flexibility to be able to avoid that. So, if someone were to consult, from the operating room to say, “I've had this constriction”, it's worth people saying, “Well, it could well be the metaraminol”. And it's worth remembering the nitroglycerin and you, and substituting a an agent such as noradrenaline may actually get you out of this situation.

STEPHEN BACCHI:            Great. Thank you very much. So for full details of the case, listeners can refer to the article which was titled “Metaraminol-induced coronary vasospasm masquerading as ST-elevation myocardial infarction during general anaesthesia”, which was published in the British Journal of Anaesthesia in 2024 with authors including Dr Joshua Kavoor, Dr Neil Warwick and Prof Pramesh Kovoor, who joined us today. Thank you again.

MIC CAVAZZINI:                 Before you skip the credits and onto your next podcast, have a go at these quiz questions. They will test how well you were listening to the case report and also connect it to your broader physician training. The questions were written by Dr Simeon Wong, who’s a member of the podcast editorial group. Here goes;

A 55-year-old male is admitted to ICU with septic shock. Despite adequate fluid resuscitation, he remains hypotensive with a mean arterial pressure of 55 mmHg. The decision is made to start a vasopressor. Which of the following mechanisms of action is most likely responsible for the effect of noradrenaline in this patient?

Any ideas? The options are;

A) Activation of β1 adrenergic receptors leading to increased heart rate and contractility 
B) Activation of α1 adrenergic receptors leading to vasoconstriction and increased systemic vascular resistance 
C) Activation of dopaminergic receptors leading to renal vasodilation and improved renal perfusion 
D) Inhibition of the renin-angiotensin-aldosterone system leading to reduced fluid retention 
E) Activation of β2 adrenergic receptors leading to smooth muscle relaxation and bronchodilation

I won’t read them all out again, but your options are β1 adrenergic receptors, α1 adrenergic receptors, dopaminergic receptors, the renin-angiotensin-aldosterone system or β2 adrenergic receptors. If you need more time to have a think, just pause the episode here.

The answer is (B) As explained by Dr Wong, noradrenaline primarily exerts its vasopressor effects through the activation of α1 adrenergic receptors, which causes vasoconstriction and increases systemic vascular resistance, leading to an increase in blood pressure. Noradrenalin also has some β1 adrenergic receptor activity, which increases heart rate and contractility, as per the first answer option, but its predominant effect in septic shock is vasoconstriction.

Okay, let’s got to question 2. A 42-year-old woman presents to the emergency department following a night out with chest pain and ST segment elevation on her ECG. She has no significant past medical history and is a non-smoker. Coronary angiography reveals no significant coronary artery stenosis. Presuming her presentation was a result of coronary stenosis due to vasospasm, which of the following is the most likely cause?

A) Cocaine use 
B) Atherosclerotic plaque rupture 
C) Cannabis use  
D) Takotsubo cardiomyopathy 
E) Hyperthyroidism

The answer is (A) Coronary vasospasm is commonly associated with cocaine use, as the drug can induce vasoconstriction via sympathetic stimulation, leading to transient coronary vasospasm. This is typically seen in patients without significant atherosclerosis.

The other options, while associated with chest pain and other coronary events, do not primarily cause vasospasm. For example, atherosclerotic plaque rupture (B) usually leads to atherosclerotic occlusion. Cannabis use (C) has a possible association with myocardial infarction but is not directly associated with coronary vasospasm.  Takotsubo cardiomyopathy (D) is characterized by left ventricular dysfunction often following stress. And hyperthyroidism (E) may cause a high output state but is not directly associated with vasospasm.

Thanks so much to Simeon Wong for those preparing questions, and of course to today’s excellent presenters, Professor Pramesh Kovoor and Dr Neil Warwick. Associate Professor Stephen Bacchi scripted the podcast with help from Dr Joshua Kovoor. We’d love to hear some feedback from RACP Trainees listening to these podcasts, so feel free to reach out at the email address podcast@racp.edu.au. And please don’t be shy about recommending it to a friend, or leaving a review at Spotify or Apple Podcasts.

This podcast was produced on the lands of the Gadigal clans of the Yura Nation. I pay respect to their elders past, present and in training. I’m Mic Cavazzini, thanks for listening.