Skip to main content
Dr. David Conen

Medical Grand Rounds featuring Dr. David Conen

Kyla Tozer, MSc Candidate (Translational Medicine)
 

Last week’s medical grand rounds were led by Dr. David Conen discussing a clinical case of perioperative atrial fibrillation. Dr. Conen is an internal cardiologist practicing in Hamilton, Ontario, and a Principal Investigator at the Population Health Research Institute at McMaster University. Dr. Conen obtained a Master of Public Health from Harvard University in Boston, USA, and a 2-year postdoctoral research fellowship in Clinical epidemiology. Currently, Dr. Conan is involved in two multinational clinical trials that focus on the preventing and treating of perioperative atrial fibrillation (AF) (COP-AF and ASPIRE-AF).

 

AF is the most common cardiac arrhythmia and is caused by an abnormal electrical pulse within the atria [1]. This irregularity can lead to abnormal blood flow within the heart and increases the risk of thrombosis and stroke [1,2]. Irregular heartbeat, shortness of breath, and diaphoresis are symptoms present in people with AF, Dr. Conen explained. AF prevention is similar to other cardiovascular diseases, and regular exercise and a healthy diet are recommended. The incidence of AF is rising in western societies, which Dr. Conen suggested that obesity and increasing cardiovascular survival may be to blame. [2]. Thus far, it has been found that increased inflammatory biomarkers high‐sensitivity C‐reactive protein and interleukin-6 are significantly associated with an increased risk of hospitalization and heart failure in patients with AF [3]. Pharmacological agents such as oral anticoagulants are a well-known preventative treatment for stroke, but how this therapy could help in perioperative AF is unknown.

 

The “Anticoagulation for Stroke Prevention in Patients with Recent Episodes of Perioperative AF After Noncardiac Surgery (ASPIRE-AF)” trial was a pilot study examining the efficacy of oral anticoagulation in the reduction of stroke and other adverse cardiovascular events, in patients with perioperative atrial fibrillation, after noncardiac surgery. Dr. Conen explained that this trial uses non-vitamin K anticoagulants as a preventative measure in a parallel assessment intervention model. 60mg of Edoxaban daily, 5mg Apixaban twice daily, 110 mg Dabigatran twice daily, or 20mg of Rivaroxaban daily are the pharmacological agents that can be used in this study. The control arm of this study is no anticoagulation unless the patient develops an indication for intervention [4]. Over the duration of this study, Dr. Conen explained patients are followed for up to 24-months and screened for adverse outcomes.

 

Finally, Dr. Conen’s discussed his clinical trial investigating anti-inflammatory agent, “Colchicine for the Prevention of Perioperative Atrial Fibrillation in Patients Undergoing Thoracic Surgery (COP-AF).” COP-AF is a placebo-controlled clinical control trial that will assess 0.5 mg of colchicine twice daily for 10 days in post-operative thoracic surgy patients. The primary endpoints are reduction of stroke and length of time in hospital.  Colchicine is an effective anti-inflammatory that has the potential to prevent perioperative atrial fibrillation post thoracic surgery [5].

 

This transitioned into some exciting news for Kingston and the surrounding area. Dr. Conen was excited to announce that as of Monday, November 15th, 2021, Kingston Health Sciences Centre will be a clinical site for the COP-AF clinical trial. This study will provide innovative care to patients in Kingston while expanding on the current research regarding AF. This study will include all patients > 55 years of age who are undergoing thoracic surgery under general anesthesia. Participants must be in sinus rhythm at the time of randomization [4].

 

After the medical grand rounds, the Translational medicine students had the pleasure of speaking with Dr. Conen about the differences in the Canadian and Swedish health care systems, the challenges and opportunities that accompany moving countries, and setting up his lab group and how he didn’t expect to end up in Hamilton, Ontario, but is happy he did. After the discussion, Dr. Conen gave some parting advice to the TMED students which focused on maintaining a passion for research.

 

On behalf of the TMED students I want to thank Dr. Conen for presenting at this week’s medical grand rounds and teaching us about the clinical trials currently in place to treat and prevent perioperative AF. We thank you for taking the time out of your busy schedule to speak with us [TMED students] about your journey and your advice on how to navigate in the competitive medical research.

 

 

References:

[1] Nesheiwat Z, Goyal A, Jagtap M. Atrial Fibrillation. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526072/?report=classic

 

[2] David Conen, MD MPH, Epidemiology of atrial fibrillation, European Heart Journal, Volume 39, Issue 16, 21 April 2018, Pages 1323–1324, https://doi.org/10.1093/eurheartj/ehy171

 

[3] Benz AP, Aeschbacher S, Krisai P, Moschovitis G, Blum S, Meyre P, Blum MR, Rodondi N, Di Valentino M, Kobza R, De Perna ML. Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation. Journal of the American Heart Association. 2021 Apr 20;10(8):e019168.

 

[4] National Library of Medicine (U.S.). (2019, May - ongoing). Anticoagulation for Stroke Prevention in Patients With Recent Episodes of Perioperative Atrial Fibrillation After Noncardiac Surgery (ASPIRE-AF). Identifier: NCT03968393. https://clinicaltrials.gov/ct2/show/NCT03968393

 

[5] National Library of Medicine (U.S.). (2017, October – ongoing). Colchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery (COP-AF) (COP-AF). Identifier: NCT03310125. https://clinicaltrials.gov/ct2/show/NCT03310125

 

Comments

Name
Nolan Breault

Mon, 11/15/2021 - 12:46

Hi Kyla,

Thank you for hosting this week's MGR discussion! In spite of the relatively short notice and additional challenge of having a guest join us over Zoom, I thought you did an excellent job of setting the scene for Dr. Conen and productively moving the conversation along. While the outcomes data of the rounds talk was very telling and highlighted the importance of conducting ASPIRE-AF and COP-AF, I found myself thinking more about a theme that was implied but not really touched on, this being sex differences.

As Dr. Conen alluded to, atrial fibrillation (AF) is predominantly a phenomenon of middle-aged and elderly individuals. Men are more likely to develop AF in general and in surgical settings, though women often report more drastic reductions in quality of life and have poorer prognoses (1-3). This is believed to partially be due to differences in average estrogen levels across a woman's lifespan, with postmenopausal women theorized to not benefit as much from the cardioprotective effects of estrogen, such as vasodilation and reduced TNF-alpha-mediated inflammation (4). Estrogen levels and their effects on signaling/the vasculature alone most likely don't account for the different presentations of AF in men and women, but it is interesting to note that this dichotomy of the sexes is precisely opposite of what is seen in pulmonary arterial hypertension (PAH), which has also been suggested to be affected by estrogen levels. With PAH, women are more likely to be given a diagnosis, yet fare better than male counterparts.

Outside of the certainly relevant lifestyle factors that differ between the sexes, such as BMI, exercise levels, and substance usage, it will be interesting to see if the therapeutic landscape for both AF and PAH evolve to consider hormonal differences. We presently have more broadly-acting approaches, such as the anticoagulants used for AF, and vasodilators for PAH, but again, this angle is interesting.

If anyone has any other thoughts on the matter, I'd be happy to discuss. Thanks again to Kyla!

Best,

Nolan

References
1. Chugh, S. S., et al. (2014) Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129:839-847.
2. Matthew, J. P., et al. (1996) Atrial fibrillation following coronary artery bypass graft surgery: Predictors, outcomes, and resource utilization. JAMA 276: 300-306.
3. Paquette, M., et al. (2000) Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation. Am. J. Cardiol. 86: 764-768
4. Ko, D., et al. (2016) Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis. Nat. Rev. Cardiol. 13: 321-332.

Name
Nolan Breault

Hi Nolan and Kyla,

You did a fantastic job managing the discussion last week, Kyla, and your summary of the MGR presented the important points in an understandable, engaging way!

Nolan, this is a really interesting topic, so I did some searching to see whether treatment for atrial fibrillation (AF) accounts for sex differences. As we talked about in the discussion, AF is treated with rate or rhythm control. Large observational cohort studies found that women had more complications related to adverse effects of antiarrhythmic drugs. This might be because healthy women tend to have longer QT intervals, and many antiarrhythmic medications prolong the QT interval. Women treated with various antiarrhythmic drugs, including sotalol and dofetilide, were more likely to develop torsades de pointes (a type of ventricular tachycardia seen in those with a long QT interval). Female patients being less able to tolerate these antiarrhythmic drugs is may be a reason why female patients treated with antiarrhythmic are less likely to return to sinus rhythm and have more AF hospitalizations (1).

We also discussed anticoagulant drugs for the treatment of perioperative AF. There is less evidence for sex differences in outcomes for patients receiving anticoagulants. Some studies have found that men experience more anticoagulation, while others have not. However, risk of stroke or embolism is similar between men and women prescribed direct oral anticoagulants (1).

I look forward to hearing your thoughts and thank you again Kyla!

Samantha

References
1. Westerman S, Wenger N. Gender Differences in Atrial Fibrillation: A Review of Epidemiology, Management, and Outcomes. Curr Cardiol Rev. 2019;15(2):136-144. doi: 10.2174/1573403X15666181205110624. PMID: 30516110; PMCID: PMC6520576.

Name
Samantha Ables

Hi Samantha and Nolan,

Thank you so much for the kind words and insightful post. Regarding your comments on sex and atrial fibrillation (AF) I find it absolutely fascinating that it is still poorly understood today [1]. I agree with you, Nolan and Samantha, in that the literature strong indicates the sex differences with AF are related to the adverse outcomes of antiarrhythmic drugs [2]. However, one of the interesting things I came across was related to health reporting. They did an observational study reviewing self-reporting on sex differences. They found that women self-report poorer outcomes than men as well. They saw that women were more likely to report poor outcomes to not only physiological outcomes, but also mental health outcomes [3]. So, Nolan, you brought up a great topic and sadly, it’s still very unclear. However, based on both of these studies, it is evident that women have poor outcomes in both physical changes caused by AF, as well as mental health outcomes.

Thank you for sharing, Nolan, and Samantha.

Kyla

References:
[1] Raisa L. Silva, Emily N. Guhl, Andrew D. Althouse, Brandon Herbert, Michael Sharbaugh, Utibe R. Essien, Leslie R.M. Hausmann, Jared W. Magnani,
Sex differences in atrial fibrillation: patient-reported outcomes and the persistent toll on women. American Journal of Preventive Cardiology. Volume 8. 2021,100252, ISSN 2666-6677,
https://doi.org/10.1016/j.ajpc.2021.100252.

[2] Andrea M. Russo, Emily P. Zeitler, Anna Giczewska, Adam P. Silverstein,
Hussein R. Al-Khalidi, Yong-Mei Cha, Kristi H. Monahan,Tristram D. Bahnson, Daniel B. Mark, Douglas L. Packer, Jeanne E. Poole, and For the CABANA Investigators. Circulation. 2021;143:661–67227 Jan 2021https://doi.org/10.1161/CIRCULATIONAHA.120.051558

[3] Linn Arvidsson Strømnes, Helene Ree, Knut Gjesdal, and Inger Ariansen. Sex Differences in Quality of Life in Patients With Atrial Fibrillation: A Systematic Review. Journal of the American Heart Association. 2019;8:e010992 Apr 2019 https://doi.org/10.1161/JAHA.118.010992

Name
Kyla Tozer

Name
Georgia

Mon, 11/15/2021 - 23:28

Hi Kyla! Great work on the summary of the presentation, and I think you did an excellent job handling the virtual question period.

I found the discussion between physicians at these Rounds particularly interesting. In addition to Dr. Conen discussing the use of biomarkers for predicting perioperative AF, Dr. Johri was also bringing up the use of non-invasive imaging as a predictive tool. Perioperative AF is associated with adverse cardiovascular outcomes, including stroke and myocardial infarction (MI) (1). Since perioperative AF is thought to be self-correcting and usually benign, it made me wonder what the follow-up of these patients is like (2). For some, this may be the first cardiac symptom they notice, and they may benefit from a more in-depth cardiovascular assessment after their surgical recovery. It seems that post-operative cardiac care for these patients involves regaining hemodynamic stabilization and organ perfusion, Beta-blockers, digoxin, or antithrombotic therapy (3). So far, I have found limited information on these patients' subsequent referrals to cardiology. Given perioperative AF's association with events, it seems reasonable for these patients to undergo outpatient monitoring through echocardiography to assess for arrhythmias, valvular issues, or coronary artery disease. This may detect risk features of stroke and MI so that more invasive interventions could then prevent the occurrence of these events. Do you think that AF patients should receive long-term cardiac follow-up, or do you see that causing undue stress on the patients and unnecessary strain on the healthcare system?

References
1. Conen, D., Alonso-Coello, P., Douketis, J., Chan, M., Kurz, A., & Sigamani, A. et al. (2019). Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery. European Heart Journal. doi: 10.1093/eurheartj/ehz431

2. Karamchandani, Kunal MD, FCCP*; Khanna, Ashish K. MD, FCCP, FCCM†,‡; Bose, Somnath MD§; Fernando, Rohesh J. MD, FASE‖; Walkey, Allan J. MD, MSc¶,# Atrial Fibrillation: Current Evidence and Management Strategies During the Perioperative Period, Anesthesia & Analgesia: January 2020 - Volume 130 - Issue 1 - p 2-13 doi: 10.1213/ANE.0000000000004474

3. Frendl, G., Sodickson, A., Chung, M., Waldo, A., Gersh, B., & Tisdale, J. et al. (2014). 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. The Journal Of Thoracic And Cardiovascular Surgery, 148(3), e153-e193. doi: 10.1016/j.jtcvs.2014.06.036

Name
Georgia

Hi Geogria,

Thank you so much for your comments and kind words. To answer your question, (1) Do I think patients should receive long-term cardiac follow-up? Personally, I do think it is important for patients to receive long-term cardiac care. How that would look may not be the same for every patient. For example, follow-up care can be through a family physician with communication to the cardiac team if needed. I think following up for mental health would also be important. If there is a clear poor outcome associated with a procedure, I think it is important to follow up in appropriate intervals. To answer your second question do I see that causing undue stress on the patients and unnecessary strain on the healthcare system? No, I don’t foresee this being issue. The reason I think this is because those patients who do not wish to be followed, simply won’t. So, the number of people who feel more comfortable being followed may be less than expected. And, as I had mentioned, this can be done through a family physician follow-up.

I hope I answered your questions appropriately.

Thank you so much.
Kyla

Name
Kyla Tozer

Name
Kiera Liblik

Tue, 11/16/2021 - 09:58

Dear Kyla,
Thank you for an excellent summary and discussion of last week's MGR. It seems that perioperative atrial fibrillation (AF) is gaining a lot of attention as of late, given the associated long-term morbidity and mortality (1-4). A recent review on the topic highlighted that age may play a role, as atrial fibrosis becomes more common with time (5). I wonder that if with enough information, we could better predict perioperative AF and, in turn, attempt to prevent it by administering anti-arrhythmic agents in the time leading up to surgery. Perhaps this could be used in conjunction with colchicine. Although, if the COP-AF trial is successful we may not need to look further!
Warm regards,
Kiera

1. Conen, D., Wang, M. K., Devereaux, P. J., Whitlock, R., McIntyre, W. F., Healey, J. S., ... & Lamy, A. (2021). New‐Onset Perioperative Atrial Fibrillation After Coronary Artery Bypass Grafting and Long‐Term Risk of Adverse Events: An Analysis From the CORONARY Trial. Journal of the American Heart Association, e020426.
2. Conen, D., Alonso-Coello, P., Douketis, J., Chan, M. T., Kurz, A., Sigamani, A., ... & Devereaux, P. J. (2020). Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery. European heart journal, 41(5), 645-651.
3. Subramani, Y., El Tohamy, O., Jalali, D., Nagappa, M., Yang, H., & Fayad, A. (2021). Incidence, Risk Factors, and Outcomes of Perioperative Atrial Fibrillation following Noncardiothoracic Surgery: A Systematic Review and Meta-Regression Analysis of Observational Studies. Anesthesiology research and practice, 2021.
4. Wang, M. K., Meyre, P. B., Heo, R., Devereaux, P. J., Birchenough, L., Whitlock, R., ... & Conen, D. (2021). Short-term and long-term risk of stroke in patients with perioperative atrial fibrillation after cardiac surgery: Systematic review and meta-analysis. CJC Open.
5. Karamchandani, K., Khanna, A. K., Bose, S., Fernando, R. J., & Walkey, A. J. (2020). Atrial fibrillation: current evidence and management strategies during the perioperative period. Anesthesia & Analgesia, 130(1), 2-13.

Name
Kiera Liblik

Name
Katie Lindale

Wed, 11/17/2021 - 20:44

In reply to by Anonymous (not verified)

Hi everyone,
Thank you Kyla for the wonderful discussion and reflections, you did a fantastic job leading our class last week. In relation to Kiera's post regarding age and atrial fibrillation (AF), I became curious about comorbidities associated with the condition. With the associations between AF and heart failure becoming increasingly common in ageing and overweight populations, we're seeing more data suggest that when these two conditions interact AF can exacerbate the morbidity and mortality of heart failure (1). Considering that about a quarter of heart failure patients have comorbid AF, and that the interactions between these two diseases are quite influential on outcomes (2), I'm interested in seeing how innovation in management of AF and perioperative AF can change the way that patients experience heart failure as well.
1. Sugumar H, Nanayakkara S, Prabhu S, Voskoboinik A, Kaye DM, Ling LH, Kistler PM. Pathophysiology of Atrial Fibrillation and Heart Failure: Dangerous Interactions. Cardiol Clin. 2019 May;37(2):131-138. doi: 10.1016/j.ccl.2019.01.002. Epub 2019 Feb 20. PMID: 30926014.
2. Lardizabal JA, Deedwania PC. Atrial fibrillation in heart failure. Med Clin North Am. 2012 Sep;96(5):987-1000. doi: 10.1016/j.mcna.2012.07.007. Epub 2012 Aug 17. PMID: 22980060.

Name
Katie Lindale

Name
Kyla Tozer

Thu, 11/18/2021 - 11:29

In reply to by Anonymous (not verified)

Hi Kiera,
Thanks so much for your thoughts on this weeks MGR. I agree with your train of thought there, in that a predictive measure for AF would be interesting. I think if there was enough understanding of the immunological impacts and risk factors, along with potential influences, we could create an algorithm to predict the risk of AF post non- and surgical procedures. I think COP-AF will be a huge asset to the Kingston Health Sciences Centre and research that can transpire here.
Thanks so much for your comments.
Kyla

Name
Kyla Tozer

Name
Trinity Vey

Tue, 11/16/2021 - 15:46

Hi Kyla,

I first want to commend you an on a great facilitated discussion and very well-written blog post! You hit all the main points from Dr. Conen’s talk which I really appreciate as someone with a limited cardiology background. In the grand round’s presentation, it was mentioned that metoprolol (beta-blockers) which are sometimes prescribed for peri-operative atrial fibrillation (POAF) inherently increase one’s risk of stroke. We rely so much on medication in the medical world, and this finding prompted me to wonder about risks associated with the other pharmacological therapies being investigated for POAF. Inevitably, certain non-vitamin K antagonist oral anticoagulants (NOAC) such as rivaroxaban are associated with risk of major bleeding (1). If patients have additional co-morbidities requiring medication, this increases the potential for adverse outcomes. Colchicine has a narrow therapeutic window with reported fatalities from 7 mg single dose administration (2). While this is much higher than the COP-AF regimen of 0.5 mg of colchicine twice daily for 10 days, over 20% of patients taking colchicine will experience diarrhea, vomiting and nausea (2). I’d imagine these symptoms could interfere with patients taking the medication twice daily. Do you think there is anything we can do to more strictly monitor or increase patient adherence during clinical trials?

I am sure that Dr. Conen’s clinical trials will further elucidate potential adverse outcomes of these medications, but it is an important reminder that all therapeutic interventions come with a cost, and that the risk-to-benefit ratio must always be considered in an individual context.

Thanks again for your great summary Kyla,

Trinity Vey

1. Pan KL, Singer DE, Ovbiagele B, Wu YL, Ahmed MA, Lee M. Effects of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2017;6(7):e005835. Published 2017 Jul 18. doi:10.1161/JAHA.117.005835
2. Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH. Update on colchicine, 2017. Rheumatology (Oxford). 2018;57(suppl_1):i4-i11. doi:10.1093/rheumatology/kex453

Name
Trinity Vey

Hi Trinity,

Thank you so much for your great post! I think you covered the clinical trials so well and pointed out some amazing things here. To answer your question, so I think there anything we can do to more stickily monitor or increase patient adherence during clinical trials? This is a great question. I think it would be amazing to have more control over compliance to ensure adherence occurs. This would improve the data and prove a very strong understanding of how the drugs are working. On the flip side, we are all human and human errors occur. I think if we had perfect adherence in clinical trials, we also wouldn’t understand how the drugs work in an imperfect scenario. So, although it would be great, I think having the human behaviours aspect to this is huge.

Thank you so much for your post, Trinity it was great!
Kyla

Name
Kyla Tozer

Name
Dilakshan Srikanthan

Tue, 11/16/2021 - 17:22

Dear Kyla,
Thank you so much for facilitating our discussion and for this wonderful summary of our Grand Rounds and subsequent discussion. One of the most interesting topics from Dr. Conen’s talk was the investigation of anti-inflammatory agents for treatment of AF. Particularly, Dr. Conen discussed the use of Colchicine for the prevention of perioperative atrial fibrillation in patients undergoing thoracic surgery. However, two recent papers on colchicine for postoperative atrial fibrillation showed conflicting results. The first showed that postoperatively-initiated adjusted dose colchicine prevented postoperative atrial fibrillation and shortened hospital stay without significant adverse effects in a double-blind randomized trial (1) while the second showed preoperatively-initiated fixed-dose colchicine failed to show reduced postoperative atrial fibrillation risk and colchicine treatment was associated with significant gastrointestinal side effects (2). Indeed further investigation is required and the different time of colchicine administration may be an important reason for the conflicting results. However, how do you think this would inform Dr. Conen’s trial and how do you think Dr. Conen’s trial can further add to the literature? Would love to hear your thoughts!

Best,
Dilakshan Srikanthan

1) Imazio M, Brucato A, Ferrazzi P, Rovere ME, Gandino A, Cemin R, et al. COPPS Investigators. Colchicine reduces postoperative atrial fibrillation: Results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. Circulation. 2011;124:2290–2295.
2) Imazio M, Brucato A, Ferrazzi P, Pullara A, Adler Y, Barosi A, et al. COPPS-2 Investigators. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: The COPPS-2 randomized clinical trial. JAMA. 2014;312:1016–1023.

Name
Dilakshan Srikanthan

Hi Dilakshan,

Thank you so much for your thought-provoking post. To answer your question, do I think the conflicting literature on colchicine treatment with AF would inform the clinical trials? I think this is a very hard question because some therapeutic interventions work differently for some people versus others. I believe there are a lot of unknowns about the causative effect of perioperative AF so predicting the outcome at this point would be almost impossible. To answer your second question, do I think this will add to the literature? Absolutely, in fact I think this is one of the most exciting aspects of the COP-AF coming to Kingston. We are going to have so much potential research and hopefully this can close the gap on dosing and treatments for AF.
I hope this answers your questions,

Thank you so much for a great post.
Kyla

Name
Kyla Tozer

Name
Cassie Brand

Tue, 11/16/2021 - 21:54

Kyla,

Excellent job leading this weeks discussion and preparing this very well thought out summary our time with Dr. Conen. As alluded to by the current perioperative AF clinical trials, effective preventative and management strategies are still being investigated. It has been suggested that classification of AF as paroxysmal (>48 h), persistent (>7 days), or permanent could help guide perioperative management (1). Perhaps this could (if not already) help guide postoperative management in preventing further cardiovascular events such as the first clinical trial you mentioned.

While management can be challenging and predictable, a focus has been placed on prevention (2). We spent most of our time learning about clinical trials pertaining to anticoagulants and anti-inflammatory agents. Dr. Conen briefly mentioned antiarrhythmic medications, which made me wonder if this is currently being investigated for prevention of perioperative AF? It was found that beta blockers administered prior to non-cardiac surgery reduced the risk of myocardial infarctions, but increased the risk of other complications (3). I would be curious to see a study on the effects of beta blockers in preventing perioperative AF, or wonder if there is a reason that beta blockers are not an area of focus for AF prevention.

Great job once again!

Best,
Cassie

(1) Liao, H. R., Poon, K. S., & Chen, K. B. (2013). Atrial fibrillation: An anesthesiologist's perspective. Acta Anaesthesiologica Taiwanica, 51(1), 34-36.
(2) Karamchandani, K., Khanna, A. K., Bose, S., Fernando, R. J., & Walkey, A. J. (2020). Atrial fibrillation: current evidence and management strategies during the perioperative period. Anesthesia & Analgesia, 130(1), 2-13.
(3) Wijeysundera, D. N., Duncan, D., Nkonde-Price, C., Virani, S. S., Washam, J. B., Fleischmann, K. E., & Fleisher, L. A. (2014). Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation, 130(24), 2246-2264.

Name
Cassie Brand

Hi Cassy,

Thank you so much for your post. I think you brought up an excellent point regarding the beta-blockers. In my opinion, I think managing any potential cardiovascular episode is important. However, for some of these individuals there aren’t any predictive measures for perioperative AF, would this be suggesting anyone who is undergoing cardiovascular surgery be placed on a beta-blocker? Do you think this would improve their quality of life? In a quick literature search I saw a paper that reviewed patients after 6-months of low-dose digoxin or bisoprolol and they saw no significant difference in quality of life [1]. However, this is something that I personally think should be investigated as perioperative AF has so many unknowns.

Great comments, very thought provoking!
Kyla

Name
Kyla Tozer

Name
Alyssa Burrows

Tue, 11/16/2021 - 22:39

Hi Kyla,

Excellent summary of Dr. Conen's lecture last week! As you mentioned, Dr. Conen is leading clinical trials looking at colchicine and non-vitamin K oral anticoagulants (NOACs) in perioperative (PO) atrial fibrillation (AF). Colchicine, an anti-inflammatory, primarily disrupts tubulin leading to subsequent downregulation of multiple inflammatory pathways and modulation of innate immunity [1]. As you addressed, this drug reduces inflammation and is a known risk factor for hospitalization and AF [2]. NOACs provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding and prevent stroke, which is also a risk factor in this patient population [3]. A study conducted with administrative data from the province of Québec found that for patients with POAF after noncardiac surgery, oral anticoagulation was not associated with a reduced risk of thromboembolic events (adjusted hazard ratio [aHR], 0.89; 95% confidence interval [CI], 0.73-1.07)[4]. The negative outcome of OACs highlights the critical need for further investigation into NOACs in this space [4].

Another therapy I was interested in that is being investigated is Sodium-glucose co-transporter inhibitors (SGLTi), which have been immensely successful in diabetics and have reduced cardiovascular outcomes, including mortality in several populations; however, their effect on AF remains unclear [5]. This meta-analysis and systemic review of SGLTi found moderate quality evidence to support a lower risk of serious AF events and a reduction in total AF events [5]. Heart failure hospitalizations and cardiovascular death were lower in patients on SGLTi [5]. In my opinion, these positive results warrant the extension of the investigation of this drug in AF to POAF. To your knowledge, are there any other drugs that may be up and coming in this space?

I am looking forward to hearing either your thoughts or anyone else who's interested!

-Alyssa

1. Leung YY, Hui LL, Kraus VB. Colchicine—update on mechanisms of action and therapeutic uses. InSeminars in arthritis and rheumatism 2015 Dec 1 (Vol. 45, No. 3, pp. 341-350). WB Saunders.

2. Benz AP, Aeschbacher S, Krisai P, Moschovitis G, Blum S, Meyre P, Blum MR, Rodondi N, Di Valentino M, Kobza R, De Perna ML. Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation. Journal of the American Heart Association. 2021 Apr 20;10(8):e019168.

3. Fanaroff AC, Ohman EM. Non-Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation. Annu Rev Med. 2019 Jan 27;70:61-75. doi: 10.1146/annurev-med-042617-092334. Epub 2018 Nov 26. PMID: 30477393.

4. McIntyre WF, Wang MK, Conen D. Balancing the Risks and Benefits of Oral Anticoagulant Use in Patients With Postoperative Atrial Fibrillation. Canadian Journal of Cardiology. 2021 Jun 1;37(6):938-e11.

5. Pandey AK, Okaj I, Kaur H, Belley‐Cote EP, Wang J, Oraii A, Benz AP, Johnson LS, Young J, Wong JA, Verma S. Sodium‐Glucose Co‐Transporter Inhibitors and Atrial Fibrillation: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2021 Sep 7;10(17):e022222.

Name
Alyssa Burrows

Hi Alyssa,
Thank you so much for your comments. I think you nailed down some incredible points that really make you think. After doing a quick literature review there are some potential candidates for these drugs, but as you had mentioned they all have moderate quality evidence to suggest a lowered risk of serious AF. And, I agree with you, it does warrant these clinical trials moving forward even if a moderate improvement is the end goal. And to answer your question, are there any drugs that may be up and coming in the space, to my knowledge Dapaglidlozin is a potential candidate for this space [1].

Thank you so much for your great post, Alyssa.
Kyla

References:
[1] Okunrintemi V, Mishriky BM, Powell JR, Cummings DM. Sodium-glucose co-transporter-2 inhibitors and atrial fibrillation in the cardiovascular and renal outcome trials. Diabetes Obes Metab. 2021 Jan;23(1):276-280. doi: 10.1111/dom.14211. Epub 2020 Oct 19. PMID: 33001548.

Name
Kyla Tozer

Name
Pierce Colpman

Wed, 11/17/2021 - 13:08

Hi Kyla thank you so much for an insightful post about Dr. Conen’s medical grand round. I was away for the discussion due to family matters as you know, and the way which you summarized this talk made me feel as if I had attended and got to learn something despite my absence.

All the clinical trials which you detailed were extremely well laid out and it seems that research regarding atrial fibrillation is in full swing both in Kingston and abroad. My question comes from the last section of your summary in which you mention the differences between Canadian and Swedish Healthcare systems. What did Dr. Conen have to say about the differences between Canada and Sweden when it comes to healthcare? Are there advantages to each, or did he think that one is superior to the other? People often colloquially praise Nordic countries for their upstanding social services and quality of life, and so it would be interesting to me to know if Dr. Conen thinks that the Swedish system is superior to the Canadian one. Secondly what is your opinion on this matter? Do you agree with Dr. Conen or do you think his opinion has bias? Again thank you for a very thoughtful summary of this medical grand round. I appreciate it a ton as it caught me up to speed on what was missed.
Best,
Pierce C.

Name
Pierce Colpman

Name
Kyla Tozer

Thu, 11/18/2021 - 11:33

In reply to by Pierce Colpman (not verified)

Hi Pierce,
Thank you so much for your wonderful post and kind words.
To answer your questions, (1) what was discussed regarding the health care systems between Canadian and Sweden? Dr. Conen pointed out it’s all the little things that are done differently that make it incredible hard to transition. So, for example, paperwork that would be done a certain way in Canada is different than Sweden. Another example is how you would bring a patient [inpatient booking] into the hospital, via the emergency room. All these little differences make it incredible tricky when moving from one place to another. On the flip side, some advantages to working in multiple settings, is that you see a vast range of cases and how they are approached. Finally, to answer your second question, do I feel the same way or is Dr. Conen’s opinion bias based on his experience? I think this question is 2-fold. One I think it would be a great experience to work in hospitals outside your resident country. Doing this would expose you to scenarios that wouldn’t be seen in your home setting (cultural differences). In my opinion, having this range of exposure strengthens you as a physician and allows you to think more broadly due to your vast range of knowledge. But, on the other side, there would be a steep learning curve regarding the bureaucracy of the healthcare system, and doing something correctly in Canada, doesn’t always translate to other countries. In my opinion, the former would outweigh the ladder. This is a wonderful question, and I am glad you touched on it.

Thank you so much Pierce,
Kyla

Name
Kyla Tozer

Name
Alyssa Burrows

Thu, 11/18/2021 - 12:21

In reply to by Pierce Colpman (not verified)

Hi Pierce,

This is a question that Trinity asked during class and I was personally interested in it because as you said Nordic countries generally are rated as happy and healthy which I also found in the lay press to be true for Sweden. Dr. Conen discussed more the differences in medical coverage and insurances. From what I gathered everyone in Sweden has to buy into a basic insurance plan. It also sounded like the medical training and residencies differ but I'm not quite sure how.

Hopefully someone else can add further to the discussion!

-Alyssa

Name
Alyssa Burrows

Name
Sophia

Thu, 11/18/2021 - 08:30

Hi everyone,

Great discussion points so far.

Dr. Conen moved from Switzerland to Canada and said he had to "re-learn" many aspects of his job in the new hospital. That being said, I am wondering if anyone can comment on the benefits of traveling abroad and how it can improve your competence as a physician and researcher in Translational Medicine.

Sophia

Name
Sophia

Name
Kyla Tozer

Thu, 11/18/2021 - 11:50

In reply to by tmedweb

Hi Sophia,
Thank you so much for starting this conversation. It is interesting because Pierce commented something similar which made me really break down how I view this. What I had mentioned, to Pierce, is that this is not a simple “good idea” or “bad idea”. Rather it is something you need to think long and hard about. My thoughts to Pierce were that doing this [traveling abroad] would expose you to scenarios that wouldn’t be seen in your home setting (cultural differences). In my opinion, having this range of exposure strengthens you as a researcher/ physician and allows you to think more broadly due to your vast range of knowledge. But, on the other side, there would be a steep learning curve regarding the bureaucracy of the healthcare system, and doing something correctly in Canada, doesn’t always translate to other countries. In my opinion, the former would outweigh the ladder. I would love to hear others’ opinions on this and if this is something they would enjoy.
Thank you so much for your post, Sophia.
Kyla

Name
Kyla Tozer

Name
Alyssa Burrows

Thu, 11/18/2021 - 12:34

In reply to by tmedweb

Hi Sophia,

Great question! His relearning seemed to centre around not knowing where equipment was and how to use electronic medical records which vary between hospitals, let alone countries. So I am sure it can be quite a steep learning curve.

I think some benefits of travelling abroad are learning different pedagogies, meeting collaborators and building your networks, different centres have different expertise, access to equipment, general resources, the opportunity to understand different populations, and social-cultural differences (such as how people eat and live and approach or interact with health care). Another example is if you go to a topical country you may get to learn about tropical diseases for example and those things might be more on your radar.

Would love to hear other people's insights!

-Alyssa

Name
Alyssa Burrows

Name
James King

Thu, 11/18/2021 - 10:36

Hi Kyla,
Thank you for an excellent facilitated discussion and blog post. You did a superb job navigating the class through a difficult topic during the facilitated discussion!
Here, I was hoping to discuss the relationship between surgery type and perioperative AF. As mentioned during the lecture, Dr. Conen stated that there are three types of surgery associated with increased risk of perioperative AF. These surgery types, in order of greatest to least risk, are thoracic surgery, major vascular surgery, and major abdominal surgery. I found this fascinating and made me wonder, why are these types of surgery associated with increased risk and not other forms of major surgery? My initial hypothesis was that these types of surgeries were done on structures located closer to the heart and that might have some relationship to the association stated above. I do think that the severity of the surgery might have some relationship as well. For example, I would not expect a minimally invasive laproscopic surgery to be associated with high rates of AF if this were true. However, this would not account for other types of major surgery, such as neurosurgery, not being listed in this group of non-cardiac surgeries associated with increased risk of perioperative AF. I did find some evidence for this second hypothesis from the realm of surgery for esophageal cancer. Patients that underwent minimally invasive esophagectomy (MIE) were at an 81% reduced risk of postoperative AF compared to those patients that underwent open esophagectomy (1). It has been reported that MIE led to lower rates of postoperative AF and, importantly, short- and long-term survival were not compromised (1,2).
I would love to hear from others regarding their take on the relationship between surgery type and perioperative AF. Has anyone else found any good studies on perioperative AF for other types of surgery?
Best,
James
1. Chen et al., 2020. The role of surgery type in postoperative atrial fibrillation and in-hospital mortality in esophageal cancer patients with preserved left ventricular ejection fraction. World J Surg Oncol. 11.
2. Chen et al., 2020. Impact of minimally invasive esophagectomy in post-operative atrial fibrillation and long-term mortality in patients among esophageal cancer. Cancer Control. 27.

Name
James King

Add new comment

Plain text

  • No HTML tags allowed.
  • Lines and paragraphs break automatically.
  • Web page addresses and email addresses turn into links automatically.