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Smallpox to COVID-19: We’ve come a long way!

The history of humankind has never witnessed an infectious agent deadlier than Smallpox. It is thought to have first appeared in Asia or Africa thousands of years ago, before spreading to the rest of the world. This virulent disease was causing hundreds of thousands of deaths each year during the 16th, 17th, and 18th centuries in Europe alone; and when Europeans brought it to Mexico in the 16th century, it killed nearly half of the previously unexposed Aztec and Inca population in less than 6 months.1,2 In the early 1700s, Lady Mary Montague, the wife of the British Ambassador to Turkey, and a disfigured Smallpox survivor, was fascinated by the smooth skin of the ladies at the famous Turkish Baths. A face with no scars was a rare sight in Smallpox-devastated England at the time. “The small-pox, so fatal, and so general amongst us, is here entirely harmless, by the invention of engrafting”, she wrote home in her notable letter.3 She had witnessed the primitive form of vaccination, which was then called inoculation. Turkish mothers would gather their children at Smallpox parties, where an old lady would tear the skin of healthy kids and smear a small sample of the virus (typically from a recently infected child). The kids would then develop a mild form of illness that recovers with no scarring and gives them long term immunity. Lady Montague used this technique to protect her son and has been credited for bringing this historical discovery back to England and advocating for its widespread use despite major opposition from the British medical community at the time (Figure 1). Subsequently, in 1796, Edward Jenner developed the much safer technique of vaccination using Cowpox instead of the Smallpox virus.4 Two centuries later, Smallpox was completely eradicated!

Figure 1: The painting Lady Mary Wortley Montagu with her son, Edward Wortley Montagu, and attendants attributed to Jean Baptiste Vanmour (oil on canvas, circa 1717). © National Portrait Gallery, London: NPG 3924.

What is most remarkable about this story is that the practice of Smallpox inoculation was introduced in Europe only in 1721 by the relentless efforts of a concerned and enlightened mother, despite being successfully used in Oriental countries such as China, India, and Turkey for centuries. In other words, one half of the globe was deeply suffering from an illness that killed millions of people over the years, while the other half held the secret to its prevention. And it was only when knowledge was exchanged between the two halves that humanity finally defeated one of its deadliest historical enemies! There has never been a better moment to relive and celebrate the magnificent product of worldly human collaboration than these days, as people around the globe started receiving their first doses of COVID-19 vaccines. A deadly virus that took the world by surprise and killed more than 1.5 million people, now, only a year later, has more than one vaccine with proven efficacy. It is amazing how far we have come along since the times of Smallpox! The obvious difference is the power of science and research, yet, another big and equally important difference, is how well connected our world is right now. This unprecedented connection is what allowed us to have a global response to this pandemic and unite our efforts to create a solution (Figure 2). Two Turkish immigrants develop a technology in the labs of a Germany-based biotech company to be quickly adopted by an American Pharmaceutical giant, which tests it and subsequently mounts a large-scale distribution process around the world —among other fascinating stories. As much as we seem deeply divided nowadays, due to political and ideological differences, in fact, over the history of humankind, there has never been a time where the world population was more united! Maybe we clearly see our major differences simply because we have never been this close! And our closeness and continued collaboration are what will get us through this! It is too early to declare victory, and things are far from perfect, but it’s a good time to pause and appreciate our progress!

Figure 2: The global effort for COVID-19 vaccine development.
Image credit: Judith Kulich, Cody Powers, Amit Pangasa, Kristyn Feldman, Parul Rewari and Samaya Krishnan. COVID-19 vaccines: Who might win the race to the global market? Published May 13, 2020. Available online on: https://www.zs.com/insights/covid-19-vaccines-who-might-win-the-race-to-the-global-market

References:

  1. Hopkins DR. The greatest killer: smallpox in history. vol. 793. University of Chicago Press; 2002.
  2. Razzell P. The conquest of smallpox: the impact of inoculation on smallpox mortality in eighteenth century Britain. Caliban Books, 13 The Dock, Firle, Sussex BN8 6NY; 1977.
  3. Lady Mary Wortley Montagu, “Lady Mary Wortley Montagu on Small Pox in Turkey [Letter],” in Children and Youth in History, Item #157. Available online: https://chnm.gmu.edu/cyh/items/show/157 (accessed December 27, 2020). Annotated by Lynda Payne
  4. Lindemann, Mary. Medicine and Society in Early Modern Europe. Cambridge University Press. p. 77. ISBN 978-0521732567; 2013.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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AHA Scientific Sessions 2020: A Preview for Electrophysiologists

AHA 2020 kicks off today in its new virtual format. As we all adjust to the new normal, many won’t have the luxury of time off dedicated to physically attending the conference. Therefore, we would likely be tuning in intermittently, in the midst of our busy schedule, to attend some of the sessions that align with our interests. With that in mind, and as an electrophysiology (EP) enthusiast, I will try to highlight some live sessions from this year’s program that should be interesting to the EP community.

Friday, November 13th

Session: Late-Breaking Science (LBS.01) – Heart Failure and Atrial Fibrillation: Vitamins, Minerals, Nutrients, and More

  • Session start time: 10:30 am (to 11:30 am) CST
  • At 11:05 am, Dr. Christine Albert will present the results of the Vital Rhythm Trial: Omega-3 Fatty Acid and Vitamin D Supplementation in the Primary Prevention of Atrial Fibrillation.

 

Session: 01 – Cardiac Procedural Innovation for Special Patient Groups

  • Session start time: 12:00 pm (to 01:00 pm) CST
  • At 12:50 pm, Dr. James Freeman will present results from the NCDR LAAO Registry regarding Patterns of Post-procedural Anticoagulation and Anti-platelet Therapy and Associated Outcomes for Watchman Left Atrial Appendage Occlusion.

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Saturday, November 14th

Session: ME.578. Atrial Fibrillation: Time for a Paradigm Shift in Management

  • Session start time: 09:00 am (to 10:00 am) CST
  • A great line-up of speakers including Drs. Andrea Russo, Jennifer Wright, Rakesh Gopinathannair, Kim-Lien Nguyen, and Prashanthan Sanders will navigate through the paradigm changes that have taken place in AF management over the past decades, including updates and novel treatment approaches.
  • The session will be moderated by Drs. Christine Albert and Jonathan Dukes.

Session: CVS.650 – Novel Technologies for Arrhythmia Detection: The Data Tsunami is Around the Corner

  • Session start time: 10:30 am (to 11:30 am) CST
  • Another wonderful group of speakers including Drs. Leslie Anne Saxon, Marco Perez, Khaldoun Tarakji, Paul Varsoy, and Janet Han will discuss the use of wearable technologies, their impact on patient management, potential medico-legal, and ethical implications, and the interface with social media.
  • The session will be moderated by Drs. Miguel Angelo Leal and Richard Page.

 Session: CVS.281. Cardiac Physiologic Pacing – When, How, and Where?

  • Session start time: 12:00 pm (to 01:00 pm) CST
  • In this interactive session, a panel of experts that includes Drs. Kalyanam Shivkumar, Pugazhendhi Vijayaraman, Weijian Huang, Daniel Lustgarten, and Mina K Chung will share their pearls on how to access the distal conduction system for pacing and will debate the role of this approach in pacing and cardiac resynchronization.
  • The session will be moderated by Drs Gaurav Upadhyay and Kimberly Selzman.

 Session: 03 – Current Challenges in Coronary and Valve Disease

  • Session start time: 12:00 pm (to 01:00 pm) CST
  • At 12:40 pm, Dr. Otavio Berwanger will present the primary results of the RIVER Randomized Trial: Rivaroxaban versus Warfarin in Patients With Bioprosthetic Mitral Valves and Atrial Fibrillation or Flutter.

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Sunday, November 15th

Session: CVS.813 – Circulation and European Heart Journal Session

  • Session start time: 12:00 pm (to 01:00 pm) CST
  • At 12:40 pm, Dr. Harry Crijns will be presenting European Heart Journal: The Year in Arrhythmias, highlighting the most prominent science published this year in EHJ in the field of cardiac arrhythmias.

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Monday, November 16th

Session: Late-breaking Science (LBS.06) – To Screen or Not to Screen, and then What? Studies of Detection and Treatment of AF

  • Session start time: 9 am (to 10:00 am) CST
  • An exciting late-breaking session dedicated to clinical trials focused on screening, monitoring, and early intervention for atrial fibrillation.
  • At 09:05 am, Dr. Subodh Verma will present the primary results of the SEARCH-AF Cardiolink Randomized Trial: Enhanced Monitoring for Atrial Fibrillation Following Cardiac Surgery.
  • At 09:13 am, Dr. Steven Lubitz will present the results of the VITAL-AF Trial: Screening for Atrial Fibrillation in Older Adults at Primary Care Visits Using Single Lead Electrocardiograms.
  • At 09:21 am, Dr. Steven R. Steinhubl will present the results of the mSToPS Trial: 3-year Clinical Outcomes in a Nationwide, Randomized, Pragmatic Clinical Trial of Atrial Fibrillation Screening – mHealth Screening to Prevent Strokes (mSToPS).
  • At 09:37 am, Dr. Jason Andrade will present the results of the EARLY-AF Trial: A randomized clinical trial of an early invasive intervention for atrial fibrillation.

Session: CVS.582 – 2020 Update on Cardiovascular Clinical Guidelines

  • Session start time: 10:30 am (to 11:30 am) CST
  • At 10:30 am, Dr. Lin Chen will be presenting Atrial Fibrillation Management in 2020, summarizing the most recent clinical practice guidelines and evidence-based care for atrial fibrillation.

Session: CVS.697 – Electrophysiology Guidelines and Expert Consensus Statements: Top 5 New Releases and Updates

  • Session start time: 12:00 pm (to 01:00 pm) CST
  • This session will cover the most important new recommendations from the EP focused guidelines that have been released in the last 2 years, namely the 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay (By Dr. Kenneth Ellenbogen), the 2019 HRS/EHRA/APHRS/LAHRS Focused Update to 2015 Expert Consensus Statement on Optimal Implantable Cardioverter-Defibrillator Programming and Testing (By Dr Martin Stiles), the 2019 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias (By Dr Usha Tedrow), the 2019 HRS Expert Consensus Statement on Evaluation, Risk Stratification, and Management of Arrhythmogenic Cardiomyopathy (by Dr Hugh Calkins) and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (by Dr. Douglas Packer).

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While there seem to be no EP-specific live sessions scheduled for that day, there will be plenty of exciting general events, including a series of COVID19-related sessions (definitely relevant to every cardiologist regardless of subspecialty). It may also be a good time to watch some of the terrific On-Demand EP sessions or simply catch up on any live EP sessions that you may have missed (should all be available to stream on-demand once presented).

I hope this was a helpful guide, and looking forward to an amazing conference and great science!

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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COVID-19 Pandemic: 5 lessons about the way we (should) debate in medicine

In my previous blog, I shared five lessons about the way we practice medicine, which I believe were highlighted by the unprecedented circumstances of the COVID-19 pandemic. I would like to share five more COVID-19-inspired reflections, but this time it’s about the way we, as physicians, debate our medical opinions and the thought processes through which we form these opinions to begin with. While these thoughts came as a result of following scientific debates on social media, I believe they apply to all sorts of debates in other contexts as well:

  1. Opinions are not principles.  Principles are ethical codes we live by and cherish for our whole life. Opinions, on the other hand, are impressions and ideas that we make as we go, based on information that is available to us (with some emotional influences as well). That being said, while it might take a major life event for someone to change their principles; opinions can, and should, change quite often. There is nothing wrong about changing one’s opinion based on new information or on changing circumstances. In fact, this only reflects a healthy and dynamic thought process. Keeping that in mind makes it easy for us to admit when we’re wrong and to accept that others are allowed to change their position without being accused of hypocrisy.
  2. Debate is not an aim. With the urge to prove our point and support our convictions, we often forget the real aim of any debate; reaching the truth through exploring alternative interpretations. Social media has opened unprecedented venues for endless debate, and the field of medicine has remarkably caught up to this. Unfortunately, we sometimes forget that proving our point often gets in the way of actually finding the truth.
  3. Absence of evidence is not evidence of absence. As physicians, we adopt a scientific thought process. We always strive to find evidence to support any medical claim. Nonetheless, it is important to remember that just because something is not supported by evidence, it does not necessarily mean that it’s not true. It often only means that “we don’t know”. In the midst of scientific debates, we tend to forget this simple fact and start to proclaim that a certain medical intervention doesn’t work simply because it hasn’t yet been assessed by clinical trials. The more accurate way to address this is to say that we don’t know if it works or not, otherwise, we would be committing the same error we were criticizing in the first place.
  4. Bias is vulnerability. Bias and prejudice are human flaws. And we are all human. We tend to be a lot less rigorous in our scrutiny of the methodology and the validity of the results of an article (scientific or otherwise) when the findings are consistent with our own bias. We tend to drop our most important defense mechanism against gullibility—our ability to think systematically and to critically appraise the evidence. This becomes particularly obvious on social media where we are quick to enthusiastically share (and sometimes praise) studies that support our viewpoints, without properly examining the content. Eliminating this bias requires a conscious effort when assessing data that align with our opinions to be even more careful.
  5. We know very little, so be humble. Every day, nature shows us that no matter how much our medical knowledge increases over time, we still know relatively very little about the world we live in. COVID-19 is just another reminder. It’s true that some of us know more than others, but in the big scheme of things, none of us is in a position to brag or be condescending. So no matter whom or what we’re debating, let’s remember to be humble, be kind, and be respectful.

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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COVID-19 Pandemic: 5 lessons about the way we practice medicine

I know that this blog was supposed to be Part 3 of the “building an academic portfolio during medical training” series, however, it’s very difficult these days to talk about anything other than COVID-19. This pandemic that has taken the whole world by storm, and reminded us all about how fragile our whole world is! Amidst all the angst and frustration, it is important to focus on positively learning from such an unprecedented experience in our lifetime. The lessons are innumerable, yet I wanted to share with you 5 points that, in my humble opinion, were highlighted by these extraordinary circumstances:

  1. Telehealth is no longer a luxury. Despite having the technology available for years, the health industry has been lagging behind when it comes to telehealth. It took a pandemic and thousands of lives for us to realize that most of the outpatient services we provide (and arguably some of the inpatient ones even) can safely be delivered virtually. The degree of disruption to one’s life and the time wasted outside the actual doctor’s visit, between taking time off from work, physically making it to the medical facility, parking, checking-in, and so forth, can easily be omitted by a technology that is readily available but we have been reluctant to use (or don’t have insurance approval to do so). There will always be a place for in-person visits, but at least we would have more time for patients that actually need to be seen in-person.
  2. Many hospitalizations and tests are unnecessary. As the pandemic worsens, physicians started to be judicious with ordering tests that require moving patients around the hospital. They also started thinking twice about who needs to be in the hospital, to begin with. We are now realizing how many tests and hospitalizations can safely be avoided, and I am hoping that we will carry these revelations with us as we move past the current circumstances.
  3. Incorporating research into clinical practice needs to be seamless. Despite major advances, the way we conduct research has not yet been optimally incorporated into our daily clinical activities. We are in desperate need to develop the necessary infrastructure that instantaneously translates patient-care input into organized data that can be used to improve the way we manage our patients. Ideally quickly enough to potentially help some of the patients who generated these data. This necessary infrastructure also extends to research regulations, which need to strike the appropriate balance between scrutiny and practicality.
  4. In a world of “evidence-based medicine”, clinical acumen remains paramount. The sudden exposure to this COVID-19 pandemic has reminded us all that often times, as physicians, we are required to operate in evidence-free zones. As much as we need to always look for evidence behind everything we do in medicine, it is essential not to forget that taking care of patients is both a science and an art. And this is why physicians can never be replaced by computers.
  5. Prevention is ALWAYS better than cure. With the great technological and pharmaceutical advances, we tend to develop great confidence in our ability to improve life expectancy. This is particularly true in procedural fields such as Cardiology. Then comes a sobering pandemic, to remind us that when it comes to public health, prevention always wins! Fortunately, we rarely need drastic measures such as quarantines and social distancing. But addressing smoking, obesity and blood pressure control will always have much more impact on our community than stents and ablations.

We will continue to learn from this world tragedy – lessons in medicine, philosophy and life in general. But, above all, this is a reminder of how noble and unique our healthcare profession is. Stay safe everyone!

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 

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Building an academic portfolio during medical training: Part 2 – finding your research team

In my previous blog, we discussed why it is important for medical students and trainees to consider research collaborations outside their own institutions, and what types of research studies can be performed using this type of collaboration between young researchers. In this blog, I will focus on how to find potential collaborators and/or join a multi-institutional team of young researchers.

Once you decide to explore this non-traditional way of doing research, the first challenge you will be facing is how to find potential research team members. At this point, you need to take a step back and ask yourself 2 essential questions:

  • “What area(s) of research am I interested in?” – This will largely be dependent on the particular specialty you are interested in pursuing as a career, and whether you have a general interest in this specialty or a more focused area that you would like to explore.
  • “What skillsets can I bring to the table in such collaboration?” – No matter how novice you are in medical research, you can always be a valuable team member provided that you are willing to learn, work hard and acquire new skills. But it is essential for you to know exactly what you can or cannot do, to be able to find your right position within a team. A successful research team requires a myriad of skills, some are basic, such as searching the literature or collecting data, some are more advanced, such as conception of research ideas or scientific writing, and others are specialized, such as relevant statistical knowledge and competency in using a statistical software or experience with using one of the databases that we previously discussed e.g. National Inpatient Sample (NIS).

Answering these 2 questions will help you present yourself in an honest and practical way to your potential collaborators, and will ensure that you achieve the 2 fundamental goals of any collaboration: to benefit and to be beneficial. It also gives you an idea about what potential skills you can work on acquiring to increase your value as a team member.

Now that you know what you want and what you can offer, it is time to find your collaborators. The easiest and most straight-forward way is to collaborate with people that you had previous experience with, like your medical school colleagues, or co-residents from your previous training program who have similar research interests. However, this may not be an available option to you, so what to do in this case? – If you are still taking your very first steps in the research field, you would be better off joining a team that is already established rather than building a new team. There are several ways to identify multi-institutional research teams that are already up and running:

  • Word of mouthyou may have heard about one or more resident or fellow who does this type of research, and in that case, you could reach out directly to them.
  • Medical literatureyou could search within your field of interest for recently published meta-analyses, systematic reviews, or articles that use one of the publicly available databases that we mentioned, and examine the authors’ list. What you would want to look for are articles that are authored by people affiliated with different institutions. Next step, would be to look up some of these authors on PubMed and see if that same group of authors (or some of them) publish these types of articles frequently together. Once you identify a particular group of collaborating authors, then you could look them up to check if they are mostly residents and fellows.
  • Social mediathis is another great tool for research collaboration. Twitter, in particular, is becoming an invaluable platform for sharing medical knowledge and recent research articles. Many of the currently active research groups promote their work on Twitter, and using the same process we just discussed, one can easily identify active members of these groups and reach out to them directly. Further, many researchers nowadays reach out on Twitter when they need young motivated medical trainees to help out with ongoing projects. So I would strongly encourage you to get on Twitter if you haven’t already done so and to start following people with similar research interests.

At this point, you know your research field of interest, you are aware of what you have to offer as a research team member, and you have identified potential research team(s) that you would like to be part of. You should be ready to reach out. What is the best way of presenting yourself? How can you maximize your chances of success in joining a team? This will be the topic of my next blog. So stay tuned…

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Building an academic portfolio during medical training: Part 1 – research outside the box

As a medical trainee in the US, whether you are pursuing an academic career or applying for a fellowship or advanced fellowship, your academic profile is one of the most important currencies you rely on for this endeavor. Academia as a general term refers to 2 main areas: research and education. Many trainees, like myself, start their residency with no or very minimal research experience. It then becomes essential to create a reasonable research portfolio during medical training, which is often not an easy task, especially in clinically demanding specialties. In this series of blogs, I will try to share some ideas and tips that can help you build a competitive research résumé during residency and fellowship. These ideas also apply to medical students, inside or outside the US, who are trying to match their dream US residency program.

The first idea that I would like to talk about is one that I thought was particularly a game changer for me when it comes to research. I like to call this one “research outside the box”, and by the box here, in addition to the abstract meaning of doing things in unorthodox ways, I’m also referring to the literal box that is the walls of your training institution. Residents and fellows are rarely involved in multicenter clinical trials or prospective studies. In fact, the vast majority of research done during medical training is retrospective observational studies. One of the main reasons trainees rely on retrospective studies is the time factor. Prospective studies often take longer to execute, and it becomes difficult to get a tangible product, a conference abstract, or a published manuscript on time for your next fellowship or job application. Therefore, retrospective studies become the more realistic option, and traditionally, these are carried out using institutional databases (i.e. clinical data from patients treated at your own training hospital), which is and will remain one of the most valuable research resources. Then comes the fundamental question – why should I consider doing research in a non-traditional way, or “outside the box”? – For many reasons:

  • Many training hospitals do not have large clinical databases that can produce impactful research projects.
  • You may not find a good research mentor in your training institution.
  • Even with available databases and good research mentors, some retrospective studies may still take long to come to fruition, sometimes longer than you can afford without a back-up plan.
  • Diversifying the ways you do research by pursuing both traditional and non-traditional means, can lead to a marked increase in productivity.
  • Most importantly, collaborating with motivated medical students, residents, and fellows around the country (and sometimes even around the globe), not only enhances your research output but is in itself a great learning and networking opportunity.

The next logical question would be – as a student or a trainee, what type of research can I do outside my institution?

For the same practical reasons that I previously mentioned, I am still referring to retrospective observational research rather than multicenter trials or prospective studies. In that case, to be able to easily collaborate with researchers across different institutions the data has to be publicly available and not protected by privacy laws. There are different types of publicly available data, some are mostly free, such as already published literature, some can be purchased for a fee, such as national and state administrative databases, and others require a research proposal that goes through a grant-like process, such as societal databases. The latter typically requires a higher degree of research expertise and are restricted by application cycles, so I would not recommend them as the first go-to option if you are still taking your very first steps in medical research. Here are some examples of observational research work that can be done collaboratively using these publicly available data sources, without being limited by institutional boundaries:

  • Published medical literature can be used for meta-analyses and systematic reviews. These types of studies commonly address hot topics in medicine or topics with controversy or equipoise. A common scenario where topics are considered “hot” is immediately after the publication of a large clinical trial, particularly if the results are not in line with prior trials on the topic. Meta-analyses are also ideal for examining uncommon side effects or complications of medications or medical procedures.
  • National administrative databases can be used to perform retrospective observational studies, e.g. the National Inpatient Sample (NIS) and the Nationwide Readmissions Database (NRD), which are commonly used in cardiovascular research. They are particularly helpful in researching rare conditions or special populations where getting a large sample size using single-center data is challenging, or to examine trends in diseases or therapies over time. Most of these databases are available for purchase per calendar year (e.g. 2010, 2011, 2012 etc.), meaning that you can buy one or more year worth of data, depending on your budget and your research question.
  • Societal databases can also be used for original outcomes and quality improvement research, e.g. the American Heart Association (AHA) Get With The Guidelines and the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) Although these do not cost money, yet, they mostly require more work including submission of a proposal during an annual or bi-annual application cycle, which is a very competitive process.

These are just examples of what can be done and some common resources that can be used to start with, but in reality, the possibilities and the available resources are endless. Now that we talked about “why” and “what”, the next question is “how” – how to reach potential collaborators? how to build a successful multi-institutional team of young researchers? And what are the challenges to this approach? This will be the topic of my next monthly AHA Early Career Voice blog. So stay tuned..

The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.

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Being an electrophysiologist has never been more exciting! Insights from AHA19

The past few years have witnessed the emergence of many technological advances that hold promises for potentially revolutionizing the way we are treating patients with cardiac arrhythmias. Between innovative technologies for cardiac pacemakers and defibrillators, breakthroughs in ablation of atrial and ventricular arrhythmias, and boundless progress in remote monitoring of cardiac rhythm, the field of clinical electrophysiology (EP) is undergoing an exhilarating conceptual transformation.

The American Heart Association (AHA) 2019 Scientific Sessions that took place in Philadelphia last month, have dedicated an excellent session to highlight and summarize these recent EP advances. A session that brought together prominent EP leaders and innovators discussing the present and the future of the field, which, to an aspiring electrophysiologist like myself, has been one of the most inspiring sessions of the conference. The title was catchy: “Hottest New EP Advances and Connections with the Experts”, and despite being an evening session, the large conference room was packed with EP enthusiasts at different stages of their careers. It was around an hour and a half of tour-de-force presentations by an outstanding group of speakers. The amount of valuable information presented is more than what can be captured in a short essay, yet, I will highlight the most promising technologies in my humble opinion.

I will start with cardiac implantable electronic devices (CIEDs), where several technological and conceptual breakthroughs have recently made their way to clinical practice, and many more are expected to do so in the near future. The 3 most exciting frontiers are:

  • The leadless intra-cardiac pacemaker system, which was approved by the FDA in April 2016. The device is the size of a large vitamin capsule, implanted percutaneously. This new technology allows cardiac pacing in the absence of intravenous leads and subcutaneous pulse generators, which not only is more convenient for patients, but also avoids lead and pocket-related complications.1 The current commercially-available system is only capable of single-chamber sensing and pacing, however, the results of the MARVEL 2 study,2 demonstrating the safety and efficacy of an accelerometer-based VDD pacing algorithm to maintain AV synchrony with the leadless pacemaker system, were just released at AHA19. Newer technologies that are expected in the next few years include atrial leadless pacemaker and leadless multicomponent systems, for instance using endocardial left ventricular electrodes as part of cardiac resynchronization therapy.
  • The new subcutaneous implantable cardioverter- defibrillator (ICD) technologies. The original subcutaneous ICD was approved by the FDA in September 2012 and has been widely used in clinical practice.3 This technology provides a defibrillator option for patients with challenging anatomy for conventional intravascular ICD implantation, and with no indication for pacing. Newer promising technologies in the field of subcutaneous ICDs that are not commercially available yet include string subcutaneous ICD – with no can, hence no need for a surgical pocket – and extravascular ICD which is capable of pacing the myocardium in addition to delivering ICD shocks, while being completely extravascular. Combining subcutaneous ICDs with leadless pacemaker systems is another exciting area of future research.
  • His bundle pacing and left bundle branch pacing, which are new physiological alternative to right ventricular pacing, and potentially to bi-ventricular pacing in patients with proximal left bundle branch block, through engaging the normal conductive His-Purkinje system and, therefore, avoiding the long term deleterious effects of ventricular dyssynchrony. As opposed to the above-mentioned technological breakthroughs, this is more of a slow ongoing learning process, which has been around since the early 2000’s, initially performed with the already-available standard pacing leads with reshaped or deflectable stylets, limited by technical difficulties. However, the more recent use of a solid core lead in conjunction with specialized sheaths has sparked new interests in this pacing technique, which is being increasingly adopted in clinical practice and eventually made its way to the most recent pacing guidelines.4 The future likely holds the development of more specialized equipment designed specifically to facilitate these pacing approaches.

 

Switching gears to the field of cardiac ablation, the other major pillar of EP interventions. The most promising, and potentially revolutionary advances in this area are:

  • Non-invasive radio-ablation of ventricular tachyarrhythmias (VT). VT ablation is known to be associated with increased risk of procedural complications given the sick phenotype that these patients commonly present with, in addition to the length of the procedure, catheter manipulations inside the left ventricle and the need for induction of VT, which makes the procedure more challenging and more risky compared to other forms of cardiac ablation. The use of stereotactic body radiation therapy (SBRT) to ablate VT in a radiology suite, aided by non-invasive cardiac mapping using electrocardiographic imaging, is undoubtedly one of the most exciting recent breakthroughs in the field of EP. The use of radiotherapy not only mitigates the procedural risks of catheter-based ablation, but also allows reaching myocardial foci that are not accessible by conventional endocardial or epicardial approaches. Although the available data are merely preliminary,5 and more research is needed prior to the widespread use of this procedure in treating patients with VT, the concept is very promising and the potential implications are remarkable. The potential use of SBRT in treating other arrhythmias such as atrial fibrillation (AF) is also under investigation.
  • Pulsed Field Ablation (PFA) for pulmonary vein isolation (PVI). Indiscriminate tissue destruction with potential damage to surrounding structures such as the esophagus and the phrenic nerve has been the major barrier to delivering reliable ablation lesions that ensure durable PVI in AF patients. This new ablation technology uses a process called electroporation, for which cardiac myocytes are most sensitive, potentially allowing selective cardiac ablation. The results of the IMPULSE and PEFCAT studies were recently published, and demonstrated an impressive 100% PVI durability at 3 months with this technique, with an average skin-to-skin procedure time of only 92 minutes. Importantly, there were no evidence of esophageal or phrenic nerve damage, despite the lack of use of an esophageal protection strategy.6 The ability to safely deliver deep ablation lesions in the atrium without damaging the surrounding extra-cardiac tissue can potentially transform the success rates of catheter ablation for AF and may expand the use of this technology to other forms of arrhythmia ablations.

 

Listening to world-renowned EP experts enthusiastically walking the audience through these various breakthroughs and painting a futuristic picture of how the world of EP can look like in the near future, left me thinking about how lucky I am to be starting my EP training in this exciting era of technological revolution. Witnessing the transformation of a cardiac subspecialty is exciting, but the possibility of being part of this transformation is mind-blowing!

 

References:

  1. Reynolds D, Duray GZ, Omar R et al. A Leadless Intracardiac Transcatheter Pacing System. N Engl J Med. 2016;374:533-41
  2. Chinitz LA, Khelae AK, Garweg C et al. Atrial Synchronous Pacing Using a Leadless Ventricular Pacemaker: Primary Results From the MARVEL 2 Study. Presented at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019
  3. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P110042. Accessed November 30, 2019.
  4. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay. Circulation. 2019;140:e382–e482
  5. Robinson CG, Samson PP, Moore KMS et al. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation. 2019;139:313–321.
  6. Reddy VY, Neuzil P, Koruth JS et al. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol. 2019;74:315-326.

 

 

The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.

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AHA19: Arrhythmia and Electrophysiology Scientific Updates

This weekend, I was fortunate to attend the American Heart Association (AHA) Scientific Sessions 2019 in Philadelphia. Based on my career interest, I was keen to attend sessions related to the field of arrhythmia and electrophysiology. While late-breaking trials such as ISCHEMIA, COLCOT and DAPA-HF have appropriately and expectedly dominated the highlights of the scientific sessions, I would like to use the next few lines to talk about a few selected arrhythmia and electrophysiology studies that were presented at AHA, and have important clinical implications in my opinion.

Early morning on Saturday, Dr Larry Chinitz from New York University Langone Health, presented the primary results of the prospective, multicenter Micra Atrial tRacking using a Ventricular accelerometer (MARVEL 2) study.1 This innovative study examined the safety and efficacy of an accelerometer-based atrial sensing algorithm in patients with atrioventricular (AV) block who are implanted with a Micra leadless pacemaker. The primary efficacy endpoint (which was available in 40 patients) was the superiority of the algorithm in providing AV synchronous pacing (i.e. VDD) compared to the conventional Micra VVI pacing. The novel algorithm was successful in maintaining AV synchronous pacing (≥70% of the time at rest, during normal sinus rhythm and complete heart block) in 95% of the patients, compared to 0% in the Micra VVI pacing (P<0.001). VDD pacing was associated with 8.8% increase in stroke volume. There were no pauses (i.e. oversensing) or episodes of pacemaker-mediated tachycardia during VDD pacing. The automatic algorithm was successful in mode switching between VVI during intrinsic AV conduction and VDD during AV block. The algorithm is not commercially available yet, however, based on this exciting data, it seems that we should expect VDD leadless pacemakers to be available in the market shortly. Furthermore, the revolutionary leadless pacing technology is likely to expand in the coming few years, with potentially atrial leadless pacemakers and multicomponent systems such as cardiac resynchronization therapy with leadless left ventricular pacemaker and the possible combination of leadless pacemaker with subcutaneous defibrillator.

Later in the day, Dr Sean Pokorney from Duke Clinical Research Institute, presented the results of the RENal hemodialysis patients ALlocated apixaban versus warfarin in Atrial Fibrillation (RENAL-AF) trial.2 The study tackles a very important question regarding the safety and efficacy of NOAC (compared to warfarin) in hemodialysis patients with atrial fibrillation and elevated stroke risk (CHA2DS2-VASc score ≥2). A total of 154 patients were randomized 1:1 to apixaban 5 mg bid (N=82, 29% received a reduced dose of 2.5 mg bid due to increased age or low body weight) or warfarin with a target INR of 2-3 (N=72). At 1-year of follow up, there was no significant difference in the primary outcome of International Society on Thrombosis and Hemostasis (ISTH) major or clinically relevant non-major bleeding between the 2 groups (31.5 vs. 25.5% for apixaban and warfarin, respectively; p > 0.05). Similarly, the secondary outcomes of ISTH major bleeding (8.5 vs. 9.7%), major intracranial (1.2 vs. 1.4%) or gastrointestinal bleeding (2.4 vs. 6.9%), stroke (2.4 vs. 2.8%) and death (25.6 vs 18.1%) were not significantly different between both groups. Dr Pokorney clarified that the study was terminated prematurely due to slower than anticipated enrollment, and that the power was limited by small sample size. However, this remains the only randomized data currently available for the comparative safety and effectiveness of NOAC vs. warfarin for non-valvular atrial fibrillation in this challenging patient population that is at increased risk of both thromboembolic and bleeding events. For the time being, it seems that apixaban is a reasonable anticoagulant option for hemodialysis patients.

Last but not least, Dr Arthur Labovitz from the University of South Florida presented the Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation (AREST) trial.3 The study was a randomized, open-label, pilot trial that included patients with atrial fibrillation who had recent cerebral ischemic symptoms (0-48 hours). The patients were randomized to apixaban (to start 0-3 days after transient ischemic attack [TIA], 3-5 days after small stroke and 7-9 days after medium stroke, N=41) or warfarin (to start 7±5 days after TIA, or 14±5 days after small or medium stroke, N=47). At 180 days, early use of apixaban resulted in less fatal stroke, recurrent ischemic stroke or TIA (19.5 vs 27.7%, p=0.46) but this did not reach statistical significance. Early apixaban use was not associated with increased risk of intracranial bleeding. The authors concluded that the early use of apixaban is safe in this patient population and may be associated with improved outcomes.

Whether you are a fan of innovative technologies that revolutionize the way we treat our arrhythmia patients, or you are an admirer of rigorous clinical trials that address common challenging scenarios in clinical electrophysiology, the high-quality science presented this year at AHA will sure satisfy your taste. Stay tuned!

 

The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.