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The Era of Misinformation: A Constant War of Science vs. Fiction

“Covid19 is a hoax”, “vaccines poison your body”, “the earth is flat.” Various conspiracy theories and misinformation statements have existed throughout history. Though some might seem absurd and often put into the spotlight to ridicule them as they are improbable to be accurate, like the earth being flat, this comedian aspect shifts to a sinister black connotation when the conspiracy theories, and misinformation infect the medical field.

As the first doctor of my family, it is not uncommon to get questions about a new drug that was promoted on TV, or regarding a bold scientific claim, such as someone curing cancer. However, during this year, amid the Covid19 pandemic, the spread of misinformation has been almost as incontrollable as Covid19 cases in the United States of America. With great concern, I saw that several acquaintances, friends, and family, most of them with higher education degrees, shared and contributed to spread false information on the treatment of Covid19, its origin, or questioning if this was part of a bigger plot to control humanity.

The spread of misinformation has contributed to mistrust towards medical healthcare personnel, to the point of being violent towards them,1  not following their advices, or falsely claiming overdiagnosis of Covid19 with the sole purpose of getting “more money,” claim that unfortunately gets backed up by the Highest Office in the Land.2

However, this problem isn’t new in the medical community, as Dr. Anne Marie Navar stated in her conference during the Scientific Sessions lecture “How Misinformation Steers Patients off Course.” She mentions that the Covid19 pandemic highlighted and made more evident the dire problem misinformation has brought to medical compliance with treatments. She focuses on the misinformation campaigns that have been occurring around statins, were social media personalities with doubtful medical claims such as the questionable Dr. Joseph Mercola, and unscrupulous social medial like Infowars pretend to scare and deter patients from taking statins, while promoting their products such as diets, supplements (Omega-3), that are commercialized with misleading labels, and lies about the efficacy of their products.

But how likely are statements made by doubtful doctors or non-healthcare providers likely to affect patient compliance? Would patients believe more something they read or see on social media than following the physician’s recommendations to whom they trust their health?  Unfortunately, it is quite likely. Dr. Navar highlights a prospective cohort study from Denmark that included 674.900 individuals > 40 years old, that were on statin therapy ( a drug used for patients with high cholesterol levels) from 1995-2010, and followed until December 31 of 2011, to test the hypothesis if statin-related news were associated with early statin discontinuation.3

This prospective cohort showed that early statin discontinuation increased with negative-statin related news, and early discontinuation was associated with increased risk of myocardial infarction and death from cardiovascular diseases (fig 1). Also, a sensitivity analysis showed that  negative statin-related news stories were associated with an odds ratio of 1.15 (CI: 1.09-1.21) for early discontinuation of antihypertensive medication (fig 2).3

Fig 1. Early statin discontinuation vs. continued use and cumulative incidence of myocardial infarction (top panel) and death from cardiovascular disease (bottom panel).

Fig 2. Statin-related news stories and early discontinuation of statin, antihypertensive medication, and use of insulin among statin users.

It is worrisome that patients’ very own life might be at stake due to misleading propaganda that feeds from the fear of exaggerating adverse events for specific treatments (drugs, vaccines, etc.). To have these very own propaganda makers, in an ungracious second act, pretending to be messiahs, to promise patients the “healthiest” option available for their disease, thus creating widely successful businesses by selling non-effective products at the expense of putting the populations’ health at risk.

But this misinformation phenomenon has been more impactful and dreadful during the pandemic since we are dealing with a highly transmissible disease, where the cost of disinformation results in more people getting infected with Covid19 ,or dying because of Covid19.

But what can we do as healthcare professionals?  As scientists? The first thing to do is to speak up. We must not be silent as false and misleading information spreads. The truth tends not to be soothing, hopeful, nor easy to process, and during this cumbersome year, this might become a more challenging task when coming to terms with “the new normal.” The evidence does not change because of our feelings, thus making it imperative to face the facts. Our role as physicians, healthcare workers, and scientists is to be modern versions of Prometheus, and reside on the frontline to fight back misinformation by being leaders that defend the torch truth, and share it with the world.

Dr. Anthony Fauci is the perfect example of the leadership we all must show as bearers of the torch of truth, as his statements are based on hard facts and science.  Nonetheless, his remarks often failed to reassure people during these unprecedented times since he has been very cautious by avoiding making any premature conclusions regarding the effectiveness of a treatment or on the efficacy of a vaccine without proper evidence, as it should be.

However, this lack of reassurance opens a door for opportunistic scientists and medical doctors such as America’s Frontline Doctors, that earlier during the year claimed that Covid19 could be treated with hydroxychloroquine, widely tested as being not useful.4,5 This bold claimed amid the uncertainty lived in the beginning of the pandemic, unleashed an incontrollable confirmation bias, as people would feel reassure when “doctors” tell them there is a cure for this virus; despite the fact that the “doctors” making such claims were not infectious disease experts, nor did they have any real evidence to support those claims. This mere example highlights the importance of raising our voices to spread real facts to prevent landslides of false information spread.

We must be empathetic to those that are sharing or commenting on false information. When seen friends or family doing this, please give them the benefit of the doubt, as people share information thinking of their well-being and that of others and, most of the time, is not out of a primary motive to harm or do wrong. When I have encountered my family or friends doing this, I try to reach out to them and ask them what they learned from the information they are sharing and explain to them the inaccuracies of all the misleading content on the news they are spreading. At last, I tell them to send me privately all the videos, chats, news they get so we can discuss them before sharing them. By doing this, the fake news chain will break, and more people will start acquiring critical thinking before sharing news from a field that is unknown or unfamiliar to their area of expertise, in this case, medical and healthcare related news.

Finally, I would like to share a pamphlet on how to fight misinformation from Dr. Tim Caufield from the University of Alberta that outlies four main steps, help stop the spread, and craft a message to counter misinformation, promote a regulatory response, and debunking (fig 3).  Let us all unite our voices so they can be loud enough to bury misinformation.


Fig 3.  Fighting misinformation pamphlet (https://www.ualberta.ca/law/faculty-and-research/health-law-institute/fighting-misinformation.html)

Acknowledgments
I would like to thank Dr. Anne Marie Navar for her conference “How Misinformation Steers Patients off Course” As it encouraged me to write todays blog on this pressing issue. I encourage you all to see her conference on the Scintific Sessions website.

References

  1. Medellin. Personal médico del Hospital General fue agredido por caso de covid-19. El Tiempo. https://www.eltiempo.com/colombia/medellin/coronavirus-en-medellin-denuncian-agresion-a-personal-medico-del-hospital-general-de-medellin-527090. Published 2020. Accessed.
  2. Griffin J. Medical professionals push back after Trump says COVID-19 cases are inflated to ‘get more money’. Daily Herald 2020.
  3. Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur Heart J. 2016;37(11):908-916.
  4. Boulware DR, Pullen MF, Bangdiwala AS, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. New England Journal of Medicine. 2020;383(6):517-525.
  5. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. New England Journal of Medicine. 2020.

 

 

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AHA 2020 Delivers on Virtual Conference Experience

As we near the close of the American Heart Association’s 2020 Scientific Sessions, I’d like to reflect on the virtual conference experience. I must admit, despite the high quality research and programming schedule, I was skeptical going into this year’s virtual conference. It was my first (of many?), and I had reservations about the ability of any organization to recreate the live experience that we all love so dearly. Looking back, the AHA put on a phenomenal show, filled with groundbreaking research, high profile panelists and even networking. For this blog, I’m going to focus on the networking, as this was the area that I was most skeptical of. How can you provide ample networking opportunities for clinicians, trainees and vendors when they’re all at home watching? Well, first, let me share the AHA’s plan to tackle this, then I’ll share some examples.

VIDEO: Networking Opportunities at AHA (Don Lloyd-Jones MD and Manesh Patel MD)

The AHA successfully delivered on their promise to fulfill the networking needs of its attendees in the following ways:

  1. AI-powered networking. The AHA brilliantly utilized burgeoning artificial intelligence technology to match like-minded individuals to each other as well as to programming that matched their interests. The AI then facilitated the organization of virtual meetings amongst interest-matched attendees. Wow!

  1. Fireside chats and FIT Virtual Lounge. The AHA continued its focus on providing mentorship to early career cardiologists and trainees. The experience was as engaging, and some would argue more engaging, than the live sessions. The democratization of commentary afforded by virtual communication was evident, as even the most reserved participants were able to ask questions and exchange ideas with established leaders in the field.

 

 

 

 

 

 

 

 

 

  1. Scavenger Hunt. Even the scavenger hunt was preserved! The AHA managed to provide a scavenger hunt experience via QR codes hidden throughout the conference programs for attendees to scan and WIN. This also further cultivated the relationship between the AHA and its industry partners.
  2. In line with its commitment to foster group wellness and health activities, the AHA organized morning yoga, exercise, and mental health sessions for attendees to virtually participate in together. This is a trend that has been popular since the start of the pandemic and hopefully will continue long after COVID-19 is gone.

In conclusion, my AHA 2020 experience has been rewarding in many ways. With quality education and networking opportunities, this year’s conference proved that the AHA is prepared to weather the challenges brought on by the COVID-19 pandemic. I look forward to future programming, and will certainly be an active participant.

 

“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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Fish Oils versus Statins?

Hypercholesterolemia remains a significant risk factor for cardiovascular disease. Management of hypercholesterolemia has entailed the use of statins and non-statins, such as omega-3 fatty acid supplements. Common side effects related to fish oil supplements have included reports of gastrointestinal upset and difficulty in swallowing the fish capsules. Common side effects of statin therapy have included reports of muscle aches, abdominal pain, dizziness, leading to non-adherence and termination of therapy.

The debate on the use of omega-3 fatty acids over statins in the management of blood cholesterol continues, calling for more studies.1  Day 3 of this year’s AHA Scientific Conference highlighted results from recent trials on the use of non-statins and statins in the reduction of cardiovascular events. Here are some takeaways from three studies: the STRENGTH Trial, the OMENI study, and the SAMSON study.

The STRENGTH (Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk Patients With Hypertriglyceridemia) trial – This phase III international study evaluated the use of a medication derived from fish oil, containing the omega-3 fatty acids EPA and DHA, more than 13,000 people who had existing heart disease or who were at high risk of heart disease due to other medical conditions.2

  • The medication did not reduce the risk of cardiac events compared to a corn oil-based placebo.
  • Atrial fibrillation, an abnormal heart rhythm, occurred more frequently in participants taking the omega-3 CA medication.

The OMENI (OMega-3 fatty acids in Elderly patients with Myocardial Infarction) trial – a study of more than 1,000 patients in Norway investigated whether adding 1.8 grams of omega-3 fatty acids to standard treatment prevented further cardiovascular events among elderly participants with recent heart attacks.

  • When compared to placebo, omega-3 fatty acids supplement in addition to statin therapy and/or a blood thinner did not reduce the number of cardiac events in the participants.

The SAMSON (The Self-Assessment Method for Statin Side-effects Or Nocebo) Trial – The study, conducted in London, enrolled adults who had previously taken one or more statins but stopped taking them due to side effects. The participants had self-reported symptoms measured throughout a 12-month period of randomly alternating months of statin use, placebo, and no medications.

  • The participants who reported side effects from statins also reported the same side effects when they unknowingly took placebo pills.
  • The side effects appeared to be mostly due to psychological rather than pharmacological effects of statins since the reported symptoms were consistent when taking the placebo.

In the discussion led by Dr. Karol E. Watson, statins remain the mainstay in the reduction of Low-Density Lipoprotein (LDL) and Atherosclerotic cardiovascular disease (ASCVD) risk.  As also recommended in the 2018 AHA/ACC/ AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol, non-statin therapies should be considered in high-risk patients with LDL above thresholds.  Heart-healthy lifestyle changes should be also considered as important measures in the reduction of LDL and triglycerides in patients at risk for ASCVD. The heart-healthy lifestyle should include diet, weight control, and physical activity.4  It will be important to observe the outcome of future studies including the combined effects of heart-healthy lifestyle interventions and non-statin/statin therapy among those considered to be at high risk for ASCVD. Future discussions should also center on intervention studies to address patients’ perceptions of statin/non-statin therapies.

 

 

References

  1. Tummala R, Ghosh RK, Jain V, Devanabanda AR, Bandyopadhyay D, Deedwania P, Aronow WS. Fish Oil and Cardiometabolic Diseases: Recent Updates and Controversies. Am J Med. 2019 Oct;132(10):1153-1159. doi: 10.1016/j.amjmed.2019.04.027. Epub 2019 May 8. PMID: 31077653.
  2. Nicholls SJ, Lincoff AM, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Pedersen TR, Ridker PM, Ray K, Karlson BW, Lundström T, Wolski K, Nissen SE. Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial. Clin Cardiol. 2018 Oct;41(10):1281-1288. doi: 10.1002/clc.23055. Epub 2018 Sep 28. PMID: 30125052; PMCID: PMC6489732.
  3. Kalstad AA, Myhre PL, Laake K, Tveit SH, Schmidt EB, Smith P, Trygve Nilsen DW, Tveit A, … Effects of n-3 Fatty Acid Supplements in Elderly Patients after Myocardial Infarction: A Randomized Controlled Trial. Circulation. 2020 Nov. https://doi.org/10.1161/CIRCULATION AHA.120.052209Circulation.
  4. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):e285-e350. doi: 10.1016/j.jacc.2018.11.003. Epub 2018 Nov 10. Erratum in: J Am Coll Cardiol. 2019 Jun 25;73(24):3237-3241. PMID: 30423393.

 

“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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Cardio-Oncology, Meet Your New Neighbor: Immunology

In this AHA session, an international group of physician scientists discussed ways to mitigate immune checkpoint inhibitor (ICI) induced myocarditis and future therapies. The session, moderated by Dr. Sakima Smith MD, MPH, FAHA (from THE Ohio State), and Dr. Doug Tiley highlighted studies by Drs. Burkhard Ludewig, DVM, Dr. Han Zhu, MD, Dr. Alcaide, PhD, Dr. Peter Liu, MD and Dr. Joe-Elie Salem, MD, PhD. The talk began with presenting the problem, basic-science T-cell mechanisms including involvement of microbiota, and ended with a possible targeted therapy, Abatacept. This is a hot topic in the cardio-oncology world considering the high mortality in those affected (up to 50%!) [1].

Source: Cardio-Oncology, Meet Your New Neighbor: Immunology| American Heart

ICIs (eg. ipilimumab, pembrolizumab) are effective targeted therapies in patients with PDL-1/PD-1 expression on tumor cells. Many cancer phenotypes are FDA approved for treatment which includes melanoma, renal cell carcinoma, non-small-cell lung cancer, Hodgkin lymphoma, and more[2]. Although these agents have shown to extend cancer survivorship[3] , they have inadvertent side effects that can lead to myocarditis and cardiomyopathy. ICIs act by “releasing the brake” of T cell immune proliferation. These monoclonal antibodies block PD1/PDL-1 ligands/receptors and allow for T cells to bind to tumor cells leading to reduced tumor burden[3]. Understanding the mechanism for ICI induced myocarditis is partially based on PDL1 knockout mice[4]. Unfortunately, there is cross-reactivity that occurs via binding to cardiac antigens (eg. myosin) leading to the inflammatory response[4].

Dr. Zhu informed us that the risk of this effect includes dual ICI treatment. In addition, early identification is key, considering 50% mortality. Patients may have a drop in their ejection fraction (EF), but have other signs of cardiac injury including brady and tachyarrhythmias. She highlighted that our current data is from FDA sponsored pharmacovigilance databases collected by Dr. Javid Moslehi, who is a pioneer and leading investigator on this subject. A registry created by Dr. Tom Neilan’s lab at Massachusetts General Hospital demonstrated an increased risk of MI and stroke after treatment with ICI[5]. Her group at Stanford along with renowned Dr. Ronald Witteles is using biobanking to identify patients with autoimmune myocarditis and controls to conduct downstream high-throughput immune repertoire analysis. Dr. Alcaide supplemented this talk by adding a novel mechanism. She discussed that reactive oxygen species (ROS) play a role in triggering downstream T cell expansion in the heart. Therefore, there may be a role in anti-oxidant therapy to reduce T cell response. Dr. Liu acknowledged our current pandemic and discussed the added risk of inflammation in the setting of concomitant COVID19 viral infection associated with myocarditis.

During this session, we learned about possible therapies to mitigate myocarditis. Dr. Ludewig discussed his teams work with an ICI mouse model. They explored T cell cross-reactivity that led to the lethality of the disease. There was a heart-gut connection! They found elevation of Bacteroides-specific CD4+ T cells in disease models which suggests that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible patients (those with HLA DQB1*03:01 polymorphisms) by showing increased reactivity against myosin 6 (MYH6) (cardiac antigen). His study suggests that the genetic susceptibility along with cross-reactivity antigens in the heart and potentially the intestine put patients at risk for fulminant myocarditis. Therefore, he proposed the use of antibiotics as a cardioprotective agent by blocking the cross-reactivity that leads to ICI induced myocarditis.

Source:  Ludewig: ‘Dangerous gut-heart liaison’| When it comes to matters of the heart, don’t always trust your gut/ Cruz et al. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science 2019; 336, 881-886.

Dr. Joe Elie-Salem (making us jealous by Zooming in from Paris; Ca alors!) ended the session with the introduction of abatacept for therapeutic use in ICI induced myocarditis.  Corticosteroids are the mainstay of treatment; however steroid therapy is nonspecific and there are unintended off-target side effects. Specifically, there is a high association with concurrent myasthenia gravis-like syndrome with ICI myocarditis that presents a challenge with the use of steroids. Steroids can lead to an exacerbation of myasthenia crisis which can lead to significant respiratory failure[6].  Based on work with Dr. Moslehi, abatacept (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] agonist, they found that in anti-CTLA4 and Anti—PDL-1  treated disease mouse models, treatment with abatacept reduced myocarditis induced death. This agent will be further explored in a Phase II trial titled: ACHLYS-trial: Phase II trial testing abatacept for ICI-myocarditis.

The take-home points for this session include: 1) ICI used to treat many cancer phenotypes are associated with incident myocarditis with up to 50% mortality 2) Cross-reactivity with cardiac antigens leads to myocyte dysfunction and the clinical sequelae of this includes cardiomyopathy (not always!) and brady/tachyarrhythmias 3) Understanding predisposing immune variants and microbiota (Bacteroides- B. theta) related to immune response associated with this disease is key to identifying all the possible therapies including antibiotics 4) Abatacept is a known T cell immunomodulator and it has a potential role in treating ICI induced myocarditis; especially in those at risk for corticosteroid effects (eg. myasthenia gravis), which will be further explored in a clinical trial.

REFERENCE

  1. Ball, S., et al., Cardiovascular Toxicities of Immune Checkpoint Inhibitors: JACC Review Topic of the Week. J Am Coll Cardiol, 2019. 74(13): p. 1714-1727.
  2. Zhou, Y.W., et al., Immune Checkpoint Inhibitor-Associated Cardiotoxicity: Current Understanding on Its Mechanism, Diagnosis and Management. Front Pharmacol, 2019. 10: p. 1350.
  3. Ferris, R.L., et al., Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med, 2016. 375(19): p. 1856-1867.
  4. Nishimura, H., et al., Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001. 291(5502): p. 319-22.
  5. Drobni, Z.D., et al., Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque. Circulation, 2020.
  6. Xing, Q., et al., Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma. Ann Transl Med, 2020. 8(5): p. 250.

“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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Buzzword Alert! Artificial Intelligence – Just the Hype Man or a Genuine Showstopper?

Conversations of the utility and promise of machine learning (ML) and artificial intelligence (AI) permeate all fields of medicine, and cardiology is no exception. A quick search shows that 69 posters containing the keywords “machine learning” made it into AHA’s Scientific Sessions 2020. But is it for real? Will we really see a future in with ML/AI factors into all aspects of clinical care and in fact, re-write the script on how we care for patients?

Below is some of the discussion points and imperatives that stood out to me today from the “Hope or Hype? Artificial intelligence and Machine Learning in Imaging.” session at #AHA20 featuring thought leaders Drs. Marielle Scherrer-Crosbie, Alex Bratt, David Ouyang, Tessa Cook, Damini Dey, David Playford, and Geoffrey Rubin.

  1. While awe-inspiring in its ability to make inferences and predictions human beings often cannot themselves, we must be aware that ML/AI algorithms can recreate and reinforce the bias pre-existing in our society. We must fight this by knowing it is a possibility, screening for it, and training algorithms on datasets that are truly representative. As much of the political landscape and national conversation right now centers on structural racism and bias in America, it’s is prudent to understand how the models we create can perpetuate this.
  1. Separate low hanging fruit from the unrealistic (at the moment) and consider the unrealistic tasks in the realm of discovery science. A quick rule of thumb provided by Dr. Ouyang, summarizing the words of Dr. Andrew Ng, first determines if it is possible for humans to do a task relatively quickly. If it is, we can probably automate it with AI now or in the near future.

  1. Scrutinize our data. How much do we trust it? High-quality data for ML/AI means broad, accurate, and plentiful. We need robust training labels, as free from subjectively as possible.
  2. How open is our data for inspection? Fields in computer science are far further along than medicine in deploying and improving ML/AI models because of open data sets and shared code, allowing groups to verify, tinker, and re-create to move the needle forward. Medical AI has not been so forthcoming.

  1. As new technology is rapidly evolving and making it into the clinical space, we need to be responsible for mistakes. This means we need to assess not only our model performance before deploying but also the consequences of using the model in real life. This may require RCTs and to consider ML/AI algorithms like we consider new therapeutics.

  1. What we really want is the AI running in the background saying “Hey, this task was automated and is now solved for you. Proceed as you see fit.” Humans and machines are in this shared space. The more we can integrate ML/AI to help us with tasks we are already doing, the better our results will be.

So where does this leave us? Most in our field believe ML/AI will play an important role in our future. Ideally, we will do it in a way that will make sure human intelligence is always paired with artificial intelligence to create a product neither of the two could be alone, will ensure our algorithms are free of bias and openly shared to allow for continuous improvement.

 

“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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Late-Breaking Highlights: “To Screen Or Not To Screen And Then What? Studies of Detection and Treatment of AF”

This was an exciting session at AHA 2020 which focused on clinical trials of screening, monitoring, and early intervention in Atrial Fibrillation (AF). Screening of AF is a controversial topic and for individuals >65 years, current AHA guidelines give a Grade 2a recommendation for screening whereas USPSTF guidelines suggest that there is insufficient evidence for screening. In this article, I will be discussing studies that addressed AF screening and their implications on clinical practice with Dr. Stavros Stavrakis who is an electrophysiologist and Associate Professor at the University of Oklahoma Health Sciences Center, Oklahoma City.

Question: What are the important goals when we think about screening for AF?

Dr. Stavrakis: The important goals for screening in AF are to establish a diagnosis of new AF in patients at high risk of stroke so they can be anticoagulated, ultimately reducing the risk of stroke.

There were 3 important trials that addressed AF screening in different patient populations.

SEARCH AF

  • In patients who have undergone cardiac surgery and have a higher risk of stroke but no history of pre-operative or pre-discharge AF, what is the risk of developing AF/Aflutter in the sub-acute post discharge period?
  • 336 post-cardiac surgery patients (median CHADS2Vasc Score 4) but with little or no AF in the post-operative period (<24 hours of AF but no intent to anticoagulate at discharge) were randomized to continuous cardiac rhythm monitoring vs usual care during the sub-acute post discharge period.
  • In the enhanced cardiac rhythm monitoring group 19.6% participants developed AF/Aflutter as compared with 1.7% in the usual care group with an absolute rate difference 17.9% (p<0.001, NNS=6).

Question: What are the implications of this trial on clinical practice?

Dr. Stavrakis: Risk of POAF, although peaking at 48-72hours post-op, is not confined to the index hospitalization, continuous monitoring for POAF can identify AF in a significant proportion of patients (20%) that may need treatment with anticoagulation. Whether anticoagulation improves outcomes in these patients, remains to be determined.

VITAL-AF Trial

  • Among older adults (age>65) presenting to primary care visits, does point of care rhythm assessment with a single lead ECG result in increased diagnosis of AF?
  • 30,722 patients were randomized to screening vs control.
  • Screening did not significantly affect AF diagnosis in the overall study sample (1.74% vs 1.60%, p=0.33)
  • Increased likelihood of AF diagnosis at primary care encounter (p<0.02)
  • Effectiveness of screening varied by age with effective screening in age>85 (risk difference 1.88%, NNS=53)
  • Overall no difference in the initiation of anticoagulation

Question: What are the implications of this trial on clinical practice?

Dr. Stavrakis: There are 2 important implications from this trial.

  1. Screening everyone age>65 for AF at a single time point is not an efficient way to detect AF, especially if the usual care is very good in detecting AF by pulse palpation or BP device.Screening at age>85 may be more effective than usual care to identify silent AF, but it is uncertain if it changes management or outcomes

mSTOPS

  • Can screening for AF by wearing an ECG patch improve clinical outcomes at 3-years?
  • 1718 actively monitored participants vs 3371 matched observational controls with analysis of 3-year clinical outcomes.
  • Mean duration of follow-up was 29 months
  • 11.4% of actively monitored patients developed AF vs 7.3% of matched controls
  • No difference in anticoagulation prescription between both arms (45.2% vs 44%, p=0.84)
  • 3-year Primary combined end point (death, stroke, systemic embolism or MI) for entire cohort was 4.5 vs 5.5 per 100 person-year (HR 0.79, p<0.01) and for diagnosed AF patients it was 8.4 vs 13.8 per 100 person-year (HR 0.53, p<0.01).

Question: What are the implications of this trial on clinical practice?

Dr. Stavrakis: Clinical outcomes can be improved with AF screening provided these patients are followed up for extended periods of time. However, this was not a randomized trial and unknown confounders may have influenced the outcome.

Question: What are 3 important unanswered questions pertinent to screening of AF?

  1. What is the impact of AF screening on clinical outcomes? Large studies, adequately powered to detect clinical outcomes, are underway (SAFER, HEARTLINE, GUARD-AF).
  2. What is the optimal screening intensity that identifies AF which would benefit from anticoagulation?
  3. What is the minimum AF burden that, if identified with screening, would benefit from anticoagulation?

“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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Late-Breaking Science Presented at AHA20

For this blog dedicated to #AHA20,  I decided to put together a list of majority of American Heart Association (AHA) late-breaking study presentations at the 2020 Virtual AHA meeting from Day 1 to Day 3. So far, the late-breaking studies at AHA have covered a wide range of topics from heart failure, cardiovascular prevention focusing on a statin, newer LDL lowering therapies, Omge-3 fatty acid supplements, to polypills and imaging in women with MINOCA. Day 4 and Day 5 will cover multiple trials on atrial fibrillation, dual SGLT inhibitor, COVID, and Telemedicine.

Day 1

Name Trials Study Population Results Conclusion
GALACTIC HF

cardiac myosin activator Omecamtiv Mecarbil In Chronic Heart Failure with Reduced Ejection Fraction: The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility In Heart Failure

Inclusion Criteria

Patients 18-85 years of age with CHF and NYHA class II, III, or IV symptoms

LVEF ≤35% and pro-BNP ≥400 pg/ml

 

N= 8256

Follow up= 21.8 months

Mean Age= 65 years

Primary Outcome=

cardiovascular death or CHF event

 

 

Mean LVEF: 27%

ACEi/ARNI  87%

Beta-blocker: 94%

Aldactone 78%

SGLT2iinhibitor: 2.5%

Primary Outcome

37.0% of the omecamtiv mecarbil group compared with 39.1% of the placebo group (p = 0.03).

 

Among patients with HFrEF on GDMT, the selective cardiac myosin activator omecamtiv mecarbil was superior to placebo. It was associated with a reduction in the primary composite outcome; however, no benefit in outcomes of CV Death, all cause death, or change in KCCQ total symptoms score.

 

AFFIRM-AHF

Ferric Carboxymaltose In Iron Deficient Patients Admitted for Acute Heart Failure

 

Inclusion Criteria

Hospitalization for CHF, and iron deficiency anemia- Serum ferritin <100 ng/ml or serum ferritin 100-299 ng/ml and transferrin saturation <20%, LVEF <50%

 

N= 1132

Follow up= 52 weeks

Mean Age= 71 yrs

Primary Outcome=

total heart failure hospitalizations and cardiovascular death

 

Primary Outcome

52.5% of the ferric carboxymaltose group compared with 67.6% of the placebo group (p = 0.059).

 

Among patients with CHF with iron deficiency, intravenous ferric carboxymaltose was associated with a numerical reduction in total heart failure hospitalizations and cardiovascular death.

 

VITAL

Omega-3 Fatty Acid and Vitamin D Supplementation In The Primary Prevention Of CV or cancer events

Inclusion Criteria

Men >50 years or women >55 years without any known known cardiovascular disease or cancer

N= 25,871

Follow up= 5.3 yrs

Mean Age= 67.1 yrs

Primary Outcome= CV death, nonfatal myocardial infarction (MI), or stroke

 

Primary Outcome

The primary CV outcome of CV death, nonfatal myocardial infarction (MI), or stroke, for vitamin D3 vs. placebo, was 3.1% vs. 3.2%, hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.85-1.1, p = 0.69.

 

The results of this trial indicate that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective in prevention of CV or cancer events

 

TIPS-3

A Polypill For Primary Prevention Of Cardiovascular Disease In Intermediate Risk People: Results Of The International Polycap Study

 

Inclusion Criteria

Target CV disease (CVD) risk: >1.0%/year

Men ≥50 years and women ≥55 years with an INTERHEART Risk Score (IHRS) of ≥10, or men and women ≥65 years with an IHRS of ≥5

 

N= 5713

Follow up= 4.6 yrs

Mean Age= 63.9 yrs

Primary Outcome= CV death, myocardial infarction (MI), stroke, heart failure (HF), cardiac arrest, revascularization

Primary Outcome

Polypill vs placebo

4.4% vs. 5.5% (hazard ratio [HR] 0.79

 

 

Once-daily polypill (fixed-dose combination of simvastatin, atenolol, ramipril, HCTZ) was superior to placebo in reducing systolic BP, LDL-C, and nonfatal CV events at approximately 5 years among intermediate CV risk patients, mostly in Southeast Asia

 

Day 2-3

 

Name Trials Topic of Interest Hypothesis Results
ALPHEUS

Ticagrelor Versus Clopidogrel In Elective Percutaneous Coronary Intervention

 

Inclusion Criteria

Patients undergoing nonemergent PCI

At least one high-risk criteria: age >75 years, renal insufficiency, diabetes, body mass index >30 kg/m2, ACS in last year, LVEF <40% and/or prior episode of heart failure, multivessel disease, need for multiple stents, left main, bifurcation or complex PCI

N= 1910

Follow up= 30 days

Mean Age= 66 yrs

Primary Outcome=

Primary Outcome

MI ype 4a, 4b (stent thrombosis) or major myocardial injury at 48 hours

 

Among patients undergoing elective and planned PCI, ticagrelor loading was not superior to clopidogrel loading. Ticagrelor failed to reduce the incidence of periprocedural myocardial infarction. Major bleeding was also similar between the groups, although an increase in nuisance or minor bleeding with ticagrelor.

 

HARP-MINOCA

Coronary OCT and Cardiac MRI to Determine Underlying Causes of Minoca in Women

 

Inclusion Criteria

prospective, multicenter, international, observational study, women with a clinical diagnosis of MI were enrolled

N= 170

145 with OCT;

116 with CMR

 

46% pts with culprit lesion on OCT.

Abnormal CMR in 74% pts, ischemic pattern in 53%, nonischemic pattern in 20.7%,

 

Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI

 

RIVER 

Rivaroxaban Versus Warfarin In Patients With Bioprosthetic Mitral Valves And Atrial Fibrillation Or Flutter: Primary Results From The RIVER Randomized Trial

 

 

Inclusion Criteria

≥18 years with bioprosthetic MV + AF/AFl without any contraindication to the AC

 

N= 1005

Follow up= 1 yr

Mean Age= 59.3 yrs

Primary Outcome= death, major adverse cardiac events, major bleeding

Mean CHAD2vASC score= 2.6, HAS-Bled Score =1.6, 18% <3 months from MV surgery, 31% >5 yrs

Primary Outcome

The mean time to the primary outcome for rivaroxaban vs. warfarin was 347.5 vs. 340.1 days (p < 0.0001 for noninferiority, p = 0.1 for superiority).

 

 

rivaroxaban is noninferior to warfarin for prevention of thromboembolic events among patients with AF/AFL and a bioprosthetic mitral valve. All strokes were lower with rivaroxaban.

 

STRENGTH

Cardiovascular Outcomes with Omega-3 Carboxylic Acids (Epanova) In Patients With High Vascular Risk And Atherogenic Dyslipidemia

 

Inclusion Criteria

Statin-treated patients ≥18 yrs with or at high risk for cardiovascular disease and TG 180-500 mg/dl, HDL <42 mg/dl (men) or 47 mg/dl (women)

 

N= 13,078

Follow up= 42M

Mean Age= 63Yrs

Omega-3 CA Dose: 4 g/day

Primary Outcome=

cardiovascular death, MI, CVA, coronary revascularization, or hospitalization for unstable angina

 

Primary Outcome met in

12.0% of the omega-3 CA group compared with 12.2% of the placebo group (p = 0.84).

 

Among statin-treated patients with dyslipidemia and high cardiovascular risk, omega-3 CA was not superior compared to placebo.

 

OMEMI

Effects Of N-3 Fatty Acid Supplements on Clinical Outcome After Myocardial Infarction In The Elderly: Results Of The Omemi Trial

 

 

 

 

 

 

 

Inclusion Criteria

Patients 70-82 years of age

With Myocardial infarction 2-8 weeks prior to randomization

 

N=1,027

Follow up= 24M

Mean Age= 74Yrs

PUFA dose: 930g EPA+ 660g DHA

Primary Outcome=

all-cause death, nonfatal MI, revascularization, CVA, or hospitalization for heart failure

 

Primary Outcome

21.0% of the PUFA group compared with 19.8% of the placebo group (p = 0.62).

 

Among elderly patients with recent myocardial infarction, PUFA was not beneficial.

 

SAMSON

A Three-arm N-of-1 Trial with Statin, Placebo And Tablet Free Periods, To Verify Side Effects And Identify Their Cause

Inclusion Criteria

Patients with any adverse event within 2 weeks of starting a previous statin

N= 60

Follow up= 12 months

Primary Outcome:

placebo symptoms divided by statin symptoms= termed nocebo ratio

 

Nocebo ratio was 0.90- meaning 90% of symptoms elicited by placebo tablets Patients with previous adverse event to statin, 90% of the symptoms could be attributed to the nocebo effect
 

EVINACUMAB

The Efficacy and Safety Of angiopoietin-like 3 (ANGPTL3) inhibitor

-Evinacumab In Patients With Refractory Hypercholesterolemia

 

Inclusion Criteria

Diagnosis of primary hypercholesterolemia (either heterozygous familial hypercholesterolemia [HeFH] or non-HeFH) with clinical atherosclerotic cardiovascular disease (ASCVD) with statin (± ezetimibe) at the maximum tolerated dose, PCSK9 inhibitor for at least 8 weeks with LDL-C ≥70 mg/dl or 100 mg/dl with or without clinical ASCVD, respectively

 

N= 160 (SC), 106 (IV)

Follow up= 16 weeks

Mean Age= 54 years

Primary Outcome=

Primary Outcome

percent change in LDL-C from baseline

 

Phase II trial

small and underpowered for clinical outcomes

 

Evinacumab is superior to placebo in reducing LDL-C among patients with refractory hypercholesterolemia despite being on statins, ezetimibe, and PCSK9 inhibitors (baseline LDL-C: ~150 mg/dl)

 

SHORT-DAPT

One Month Dual Antiplatelet Therapy Followed By Aspirin Monotherapy After Drug Eluting Stent Implantation

Inclusion Criteria

Patients ≥19 years of age

undergoing PCI for stable or unstable ischemic heart disease

AMI excluded

 

N= 3020

Follow up= 12 months

Mean Age= 67 yrs

Primary Outcome=

cardiac death, nonfatal myocardial infarction, target-vessel revascularization, stroke, or major bleeding at 12 months

 

Primary Outcome

5.9% of the 1-month DAPT group compared with 6.5% of the 6- to 12-month DAPT group (p for noninferiority < 0.001; p for superiority = 0.48).

 

Among patients undergoing PCI for stable or unstable coronary artery disease, 1 month of DAPT was noninferior to 6-12 months of DAPT

 

 

“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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FA… wha? Oh… FAHA! Becoming a Fellow of the American Heart Association (FAHA)

Curious about what a Fellow of the American Heart Association (FAHA) was, I attended the “Journey to becoming FAHA” panel discussion this afternoon to learn more from Dr. Annet Kirabo (Vanderbilt University), Dr. Nasrien Ibrahim (Massachusetts General Hospital), Dr. Swapnil Hiremath (Ottawa Hospital Research Institute), and Dr. Antonio Cabrera (University of Utah). Collectively, this panel covered many topics for the FAHA curious. Below are some of the major questions answered.

What is a FAHA and how do I become one?

Broadly speaking, a Fellow of the American Heart Association (FAHA) is a physician, scientist, nurse, or other healthcare professionals that has made sustained contributions to the field of cardiovascular disease and/or stroke. General FAHA requirements include a history of AHA membership (i.e.being an AHA partner for at least two years), holding a Premium Professional or Premium Professional Plus membership, possessing an affiliation with one of the 16 AHA Scientific Councils, and a letter of recommendation from an existing FAHA member. However, each Scientific Council has an additional set of FAHA criteria that must be met for a successful application, so do your research and make sure you qualify. Each year, there are two FAHA application due dates, meaning there are many opportunities to apply. To learn more, check out the American Heart Association (AHA) website: https://professional.heart.org/en/partners/fellow-of-aha.

What are the benefits of becoming a FAHA?
As stated on the AHA website, the many benefits of becoming a FAHA include free online access to AHA journals, priority registration for AHA Scientific Sessions, and reduced registration fees to AHA meetings. However, all of the panelists highlighted the additional networking benefits of being a FAHA that have helped them in their early careers. Dr. Cabrera specifically noted that the AHA is an excellent source of role models and mentors for both scientists and clinicians. In addition, Dr. Ibrahim noted that being a FAHA has been helpful for her research, with networking ultimately resulting in more publication and speaking opportunities.

How can I showcase my commitment to the AHA? What kinds of AHA service opportunities are there?
To successfully become a FAHA means showing sustained commitment and service to the AHA. Thankfully, the AHA makes this easy. As Dr. Kirabo noted, on the AHA website you can fill out the Science Volunteer Form to receive emails with volunteer opportunities. In addition, Dr. Ibrahim promoted the AHA Early Career and FIT Blogging Program, which initially allowed her to amplify her voice in the cardiovascular health and clinical cardiology fields.

If I am not a researcher, does a lack of published paper prevent you from becoming a FAHA?    

Depending on the Scientific Council you are applying to, a lack of publications can play a role. However, Dr. Cabrera noted that there is a great deal of variation in assessing productivity and scholarship and that the AHA tries to create opportunities for teachers and clinicians (not only research scientists) by assessing achievement using criteria beyond publications.

If I applied but was not approved to be a FAHA the first time, what should I do? How can I improve my chances?
Check the criteria for becoming a FAHA. Check with a FAHA on your Scientific Council and determine where the gap is and how it can be filled. Most importantly, don’t give up — try again!

Do you have any last pieces of advice for FAHA applicants?

Use your two years of required AHA membership to build up your AHA service — most importantly, commit this service to something you are genuinely interested in. Get a solid personalized letter of recommendation from an existing FAHA member for your application. Lastly, don’t hesitate, just do it.

 

Find out more about FAHA: https://professional.heart.org/en/partners/fellow-of-aha

“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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An ALL-Woman Trial on MINOCA Takes a Seat in the Main Area as Late Breaking Science Addressing Challenges in Coronary Care

As an interventional cardiologist who’s passionate about reducing the disparities in diagnosis and management in women with cardiovascular disease, I was captivated by the late-breaking science that took the main arena for Current Challenges in Coronary and Valve Disease at Scientific Sessions 2020. The Coronary OCT and Cardiac MRI (CMR) to Determine Underlying Cause of MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries) in Women Trial from the HARP (Women’s Heart Attack Research Program) investigators led by Dr. Reynolds and colleagues is truly groundbreaking for women patients with MINOCA (1).  HARP-MINOCA was a multimodality imaging trial that included all women. Yes—that’s correct. An ALL Woman Trial. Why would a study enroll all women?  Because MINOCA is a condition that disproportionately affects women (3). In women presenting with MI, the presence of MINOCA is 10.5% compared to 3.4% in men (4).  MINOCA is a disease process that has largely been met with controversy such that clinicians have challenged the presence of a “true” myocardial infarction in the absence of coronary artery disease. Furthermore, the lack of an obstructive lesion on a coronary angiogram has misled women to believe that they’re “fine” just because their coronary arteries don’t require stenting.  This is completely false. Patients with MINOCA have clinical outcomes similar to patients with obstructive CAD at the time of myocardial infarction (MI) (3).  Our patients have suffered in this variability of treatment and assessment which ultimately impacts their care. The findings of this study area additive to the American Heart Association’s scientific statement on the contemporary diagnosis and management of MINOCA which sought to standardize the definition of MINOCA and create a clinically useful diagnostic framework and treatment algorithm (2). Thus, the HARP-MINOCA multimodality imaging findings deepen the roots of MINOCA as a true disease process that requires a proper diagnosis with multimodality imaging to optimize management for improved patient outcomes.

This prospective multicenter study enrolled women a total of 301 women with a clinical diagnosis of MI across 16 different sites of which 170 had MINOCA. Once invasive coronary angiography was performed and revealed <50% stenosis in all major arteries, multi-vessel optical coherence tomography (OCT) was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). [Figure 1]

Figure 1

Dual imaging allowed for a thorough investigation of the following: 1) Vascular causes of MINOCA by OCT, 2) Myocardial abnormalities on CMR and 3) integration of the various underlying etiologies on OCT and CMR.  The findings from OCT investigation revealed that a culprit lesion in 46% of cases included plaque rupture, thrombus without plaque rupture, intra-plaque cavity, layered plaque, dissection, or spasm.  The CMR findings revealed infarction with late gadolinium enhancement 33% of cases, regional pattern of ischemic injury in 21% and 21% had non-ischemic pattern giving them an alternate diagnosis. The study did have a few limitations included a low rate of STEMI enrollment, regional myocarditis cannot be excluded from the CMR definition of ischemic injury (defined as a single coronary territory with myocardial edema) that was used, the contribution of coronary vasospasm to the presentation was not evaluated, and not all women underwent 3-vessel OCT and CMR leaving some diagnoses that may have been missed.

The integration of the dual-imaging findings revealed a specific cause for MINOCA in 85% of cases.  When an OCT culprit lesion, there was CMR evidence of infarction or regional ischemic injury in 75% of cases.  Multi-modality imaging was better than either imaging modality alone leading to an identified cause of MINOCA in 85% of cases. One of the cases shared during the trial presentation was eye-opening.  Despite no evidence of an obstructive lesion in the LAD vessel on a coronary angiogram, OCT performed in the LAD revealed plaque rupture and subsequent CMR demonstrated a small, transmural infarction in the terminal segment of the LAD. [Figure 2]. The importance of establishing the diagnosis with additional multimodality imaging is the key findings here. MINOCA patients have pathophysiology hidden deep beyond the limitations of coronary angiography and without additional imaging, they could be subject to a missed diagnosis and ultimately poor long-term care and management.

Figure 2

The 2020 European Society of Cardiology for non-ST elevation MI gave the use of CMR a Class IB recommendation for MINOCA evaluation.  Unfortunately, there are no such recommendations for the use of intracoronary imaging. As a community-based interventionalist who performs emergent percutaneous coronary interventions at ST-Elevation MI (STEMI) receiving centers without cardiothoracic surgical support, we have restrictions as operators when performing interventions such an intravascular imaging when no intervention is planned.  The implications of this OCT relevant data would be practice-changing for interventional cardiologists practicing in my clinical setting.  The feasibility of OCT may bring its own challenges with operator-experience, staff support, and contrast use.  However, education regarding the important data noted from OCT in MINOCA patients is a very important first step to implement change in one’s cath lab.

This study presented here at sessions continues to advance the growing field of MINOCA science. Late-breaking science advancing the understanding of this heterogeneous population of MINOCA patients is incredibly exciting and I’m looking forward to the continuum of knowledge to transform the algorithm for diagnostic assessment and framework for MINOCA treatment.

 

 

References:

  1. Reynolds et al. Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of MINOCA in Women. Circulation 2020; Epub. 10.1161/CIRCULATIONAHA.120.052008
  2. Tamis-Holland JE et al. Contemporary diagnosis and management of patients with myocardial Infarction in the absence of obstructive coronary artery disease: a scientific statement from the American Heart Association. Circulation. 2019;139(18):e891–908.
  3. Safdar B et al. Presentation, clinical profile, and prognosis of young patients with myocardial infarction with nonobstructive coronary arteries (MINOCA): results from the VIRGO study. J Am Heart Assoc. 2018;7(13)
  4. Smilowitz NR et al. Mortality of myocardial infarction by sex, age, and obstructive coronary artery disease status in the ACTION registry-GWTG (acute coronary treatment and intervention outcomes network registry-get with the guidelines). Circ Cardiovasc Qual Outcomes. 2017;10(12):e003443.

“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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Late-Breaking Highlights: Fish Oils and Frustrations in Lipid Management

It was another exciting day of virtual sessions at #AHA20, led by intriguing findings from a few late-breaking trials!

 

First, the STRENGTH and OMEMI trials added nuance to ongoing discussions about the cardiovascular benefits of fish oils and cardiovascular risk reduction. The REDUCE-IT trial, published in the New England Journal of Medicine (NEJM) in 2019, showed that the highly purified fish oil icosapent ethyl improved cardiovascular outcomes in high-risk participants who had elevated triglycerides despite statin therapy. The STRENGTH and OMEMI trial, however, may temper enthusiasm about the use of fish oils in high-risk patients.

 

The STRENGTH trial randomized 13,000 participants in 22 countries to an omega-3 carboxylic acid or corn oil placebo, with a primary endpoint of cardiovascular death, myocardial infraction, stroke, coronary revascularization or hospitalization for unstable angina. The trial was stopped early due to “futility,” though it still achieved 1580 of the target 1600 endpoints needed for results to be sufficiently powered. Compared with those receiving corn oil placebo, participants in the omega-3 fatty acid group experienced a 19% reduction in triglycerides, 20% reduction in C-reactive protein and 269% increase in plasma eicosapentanoic acid (EPA; icosapent ethyl is a highly purified and stable version of this fatty acid). Despite these biochemical differences, there was no difference in the primary outcome between the two groups, 54 months after randomization. The major adverse outcome, atrial fibrillation, was significantly more likely in the treatment arm.

 

Why do STRENGTH findings differ from those of REDUCE-IT? STRENGTH and REDUCE-IT participants had similar triglyceride levels, but patients in the STRENGTH intervention arm had lower EPA levels than those in the REDUCE-IT treatment arm. Moreover, REDUCE-IT contained more participants with established CAD. Additionally, STRENGTH used a corn oil placebo, while REDUCE-IT used a mineral oil placebo. Corn oil has been shown to have a neutral effect on triglycerides and potentially some cardioprotective effects, while mineral oil may result in unfavorable increases in triglycerides and LDL. Some may argue that the use of mineral oil in REDUCE-IT might have exaggerated the efficacy of icosapent ethyl.

 

The OMEMI trial, meanwhile, randomized 1,000 elderly, 70-82 year old patients (who had had a myocardial infarction [MI] in the 2-8 weeks prior to enrollment) to 1.8 grams of omega-3 fatty acids or a matching corn oil placebo for 2 years. It excluded participants who could not tolerate fatty acids or who had diseases that would impact their ability to survive the 2 year study period. OMEMI found no difference in the composite primary outcome (non-fatal MI, unscheduled revascularization, stroke, hospitalization for heart failure or all-cause death). There were no significant differences in key clinical subgroup analyses, and there was a greater (though not statistically significant) risk of atrial fibrillation in the treatment arm. There was no difference in major bleeding.

 

Taken together, findings from STRENGTH and OMEMI complicate the picture of fish oil utilization and raise further questions about whether the cardiovascular effects of fish oils in some populations are beneficial or neutral. More work needs to be done to better elucidate the effects of fish oils on cardiovascular risk reduction in high-risk patients.

 

Nevertheless, while STRENGTH and OMEMI made waves owing to their potential practice-changing implications, I left the day feeling particularly inspired by the SAMSON trial. This ingeniously designed trial enrolled 60 participants who had stopped taking statins due to symptoms arising within two weeks. Any symptom was eligible if it was severe enough to lead to statin discontinuation in that time span. The most common symptoms were muscle aches, fatigue, and cramps. Participants were given four bottles containing atorvastatin 10 mg tablets, four bottles containing placebo pills and four empty bottles. Each month, they were randomly assigned to take the contents of one of the bottles, in a crossover fashion, with no washout between months. They were asked to rate the severity symptoms they experienced using a mobile phone app. They were also asked 6 months after the conclusion of the trial if they had resumed taking statins. Investigators combined symptom ratings, reporting average symptoms levels during “statin”, “placebo” and “no treatment” months.

 

SAMSON found that the severity of symptoms reported was substantially higher during statin months than during no treatment months; however, this was also true for placebo. Reported symptom levels during statin and placebo months were no different from each other. The nocebo proportion was 0.9; that is, 90% of symptoms reported during statin months were elicited by taking placebo tablets as well. Even more importantly, half of the participants resumed statins again after the trial!

 

SAMSON serves as a lesson to aspiring cardiovascular researchers that even a small study can have a major impact. It displays respect and empathy for the patient experience by acknowledging rather than denying that patients do experience side effects from statins. However, it also strongly suggests that these symptoms may be attributable to the act of taking a pill rather than the medication content of the pill itself. Lastly, SAMSON proves that patients who realize that statin side effects may not actually be specific to statins themselves may be willing to resume taking statins. These findings further support the foundational concept that we as physicians must respect our patients by engaging them in shared decision-making and give patients an opportunity to understand the science, rather than simply telling them what to do.

“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.”