Blog – Page 4 – The Early Career Voice

Climate Change and Cardiovascular Diseases

March 16, 2022March 22, 2022 Gaganpreet Kaur

Climate change is partly due to the increased atmospheric concentration of greenhouse gases emitted by burning fossil fuels like oil, natural gas, and methane produced by ruminant agricultural animals. The earth’s temperature has augmented by 0.85°C in the last century, and the rate of global warming has increased to 0.18°C/decade in the last three decades. The altering temperature, in particular increasing heat, is one of the critical features of climate change and can significantly affect cardiac health. In addition, extreme weather events, rising sea levels, and lack of food and water are expected outcomes of climate change¹.

Cardiovascular Diseases (CVDs) are the leading cause of death globally, and climate change can worsen CVD incidence further. Heatwaves are expected to be more frequent and prolonged due to ongoing climate change. The intense heat can cause mortality and morbidity due to heatstroke, which is defined as hyperthermia associated with a systemic inflammatory response resulting in multiple organ failure and predominant encephalopathy. Heat stress is associated with acute cardiac events where heated blood circulates in peripheral circulation, and heat tolerance is impaired due to insufficient cardiac output to meet the body’s needs for sufficient heat loss¹.

There is a U-shaped relationship between temperature and all-cause mortality where mortality increases with the shift from ‘optimum temperature’ at both cold and hot ends. In the Netherlands, the lowest mortality rate was observed with an average temperature of 16.5°C, and CVD mortalities accounted for 57% of cold-related death². In 1976, daily deaths from coronary thrombosis increased two-fold during the London heatwave³. Additionally, daily mortality due to congestive heart failure is strongly associated with maximum daily temperature in Montreal, with an exponential increase starting at 25°C⁴. Similarly, during comparatively hotter summer, a U-shaped relationship between outer temperature and coronary artery disease deaths is reported in Taiwan⁵.

Lifestyle modifications on a large population scale are required to reduce the emission of greenhouse gases, thereby mitigating the extent of climate change. Reducing the use of motor vehicles for short-distance commuting can help reduce the emissions of greenhouse gases related to transportation and air pollution that can have adverse effects on health. Further, reducing the consumption of ruminant meat such as sheep and cows and increasing the use of renewable energy, including solar radiation or wind power, can help mitigate climate change, air pollution, and the risks of heart diseases¹.

Another essential remedy to diminish climate change can be ‘active transport or self-transport that encompasses more physical activity and involves walking, cycling, and use of public transport as a mode of transportation. This will not only reduce the emanation of greenhouse gases but increased physical activity can confer several cardiac health benefits¹. An extra kilometer walk is associated with a 4.8% reduction in risk of obesity which is a significant risk factor of CVD, whereas an extra hour spent in car/day is lined with a 6% increase in the likelihood of obesity⁶. Additionally, a study done in Finland reported a significant reduction in CVD risk and all-cause mortality in women who walked or cycled 15 minutes or more for work⁷.

In conclusion, we need to modify our lifestyle and make healthier choices to protect our hearts and earth. If you are further interested in the topic, you can get a detailed insight in the review article published in the Cardiology journal¹ titled “The effects of climate change on cardiac health”.

REFERENCE

De Blois J, Kjellstrom T, Agewall S, Ezekowitz JA, Armstrong PW, Atar D. The Effects of Climate Change on Cardiac Health. Cardiology. 2015;131(4):209-17. doi:10.1159/000398787
Kunst AE, Looman CW, Mackenbach JP. Outdoor air temperature and mortality in The Netherlands: a time-series analysis. Am J Epidemiol. Feb 01 1993;137(3):331-41. doi:10.1093/oxfordjournals.aje.a116680
Keatinge WR, Coleshaw SR, Easton JC, Cotter F, Mattock MB, Chelliah R. Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis. Am J Med. Nov 1986;81(5):795-800. doi:10.1016/0002-9343(86)90348-7
Kolb S, Radon K, Valois MF, Héguy L, Goldberg MS. The short-term influence of weather on daily mortality in congestive heart failure. Arch Environ Occup Health. 2007;62(4):169-76. doi:10.3200/AEOH.62.4.169-176
Pan WH, Li LA, Tsai MJ. Temperature extremes and mortality from coronary heart disease and cerebral infarction in elderly Chinese. Lancet. Feb 11 1995;345(8946):353-5. doi:10.1016/s0140-6736(95)90341-0
Frank LD, Andresen MA, Schmid TL. Obesity relationships with community design, physical activity, and time spent in cars. Am J Prev Med. Aug 2004;27(2):87-96. doi:10.1016/j.amepre.2004.04.011
Barengo NC, Hu G, Lakka TA, Pekkarinen H, Nissinen A, Tuomilehto J. Low physical activity as a predictor for total and cardiovascular disease mortality in middle-aged men and women in Finland. Eur Heart J. Dec 2004;25(24):2204-11. doi:10.1016/j.ehj.2004.10.009

“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 health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”

Inflammation: a missing target in coronary heart disease treatment

March 14, 2022March 22, 2022 Reza Mohebi, MD

The role of inflammation in coronary artery disease’s pathophysiology dates back to more than 100 years ago. By the end of the 18^th century, Virchow described atherosclerosis as “endarteritis deformans” for the first time. Since then, many studies at the cellular level have shown that lipid accumulation in blood vessels cannot justify the development and progression of the atherosclerosis process. Today, it is established that metabolic factors in conjunction with the inflammatory process lead to the initiation and progression of atherosclerosis. Still, the interaction of innate and adaptive immune systems for the development of atherosclerosis is not fully understood.

Despite significant progress in cardiovascular disease therapies, patients with cardiovascular disease are at high risk of adverse clinical outcomes. Current treatments have focused on lowering low-density lipoprotein-cholesterol concentration, inhibiting platelet activation and coagulation cascades, controlling blood pressure and glucose levels. None of these FDA-approved therapies have targeted the inflammatory pathways involved in atherosclerosis.

Clinical studies have emerged in the cardiovascular field to target inflammation in the past five years. Canakinumab, a monoclonal antibody targeting interleukin-1β, was one of the first anti-inflammatory medications shown to lower the risk of adverse cardiovascular events. In 2017, Ridker and colleagues¹ showed that canakinumab led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering among patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. Two years later, in 2019, Ridker and colleagues² published the efficacy of low-dose methotrexate to prevent atherosclerotic events. Unlike the Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS), methotrexate-an antimetabolite medication indicated for the treatment of autoimmune diseases and a variety of cancers- not only failed to show any efficacy in lowering adverse cardiovascular events among patients with previous myocardial infarction or multivessel coronary disease but also resulted in elevations in liver enzyme levels, reductions in leukocyte counts, hematocrit levels, and a higher incidence of non–basal-cell skin cancers than placebo. The negative result implies the need for explicitly targeting the inflammatory pathways directly involved in atherosclerosis. In 2020, 2 studies evaluated the efficacy of colchicine in reducing atherosclerotic events. Both studies^{3, 4} showed that patients with chronic coronary artery disease who received colchicine 0.5mg daily had a lower risk of cardiovascular events compared who received placebo. Lastly, a double-blind, randomized, placebo-controlled phase 2 trial⁵ evaluated the efficacy of ziltivekimab-a human monoclonal IL-6 inhibitor- among chronic kidney disease patients with elevated high-sensitivity CRP. The study showed that ziltivekimab significantly reduced biomarkers of inflammation relevant to atherosclerosis. The study paves the way for conducting a large-scale cardiovascular outcomes trial to investigate the effect of ziltivekimab at high risk of cardiovascular events.

In today’s practice, monoclonal antibodies targeting interleukins are standard therapies in many medicine subspeciality like oncology (many cancers: lymphoma, leukemia), rheumatology (autoimmune disease: rheumatoid arthritis, gout), gastroenterology (Crohn’s disease), and infectious disease (COVID-19 treatment). In the cardiovascular field, although randomized trials are emerging about the efficacy of monoclonal antibodies targeting inflammatory pathways to reduce the cardiovascular risk in patients with atherosclerotic disease, still further evidence is needed. The role of inflammation in atherosclerosis is well-established, and cardiologists may need to better familiarize themselves with inflammatory pathways involved in atherosclerosis since many anti-inflammatory medications will probably be routinely prescribed in the near future to lower the elevated cardiovascular risk.

References:

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ and Group CT. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377:1119-1131.
Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, Hasan A, Rosenberg Y, Iturriaga E, Gupta M, Tsigoulis M, Verma S, Clearfield M, Libby P, Goldhaber SZ, Seagle R, Ofori C, Saklayen M, Butman S, Singh N, Le May M, Bertrand O, Johnston J, Paynter NP, Glynn RJ and Investigators C. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019;380:752-762.
Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L’Allier PL, Guertin MC and Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381:2497-2505.
Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL and LoDoCo2 Trial I. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383:1838-1847.
Ridker PM, Devalaraja M, Baeres FMM, Engelmann MDM, Hovingh GK, Ivkovic M, Lo L, Kling D, Pergola P, Raj D, Libby P, Davidson M and Investigators R. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomized, placebo-controlled, phase 2 trial. Lancet. 2021;397:2060-2069.

Afraid of What’s in Vaccines? Here Are 5 Things You Ingest or are Exposed to Everyday Without Thinking Twice About Their Effects on Your Body and Heart Health

March 7, 2022February 22, 2022 Kyla Lara-Breitinger, MD

The American divide regarding the COVID-19 vaccine is a passionate topic for everyone. This article is not intended to prove to readers why getting vaccinated for COVID-19 is safe but to provide some insight on the daily decisions we don’t think twice about that have both theoretical and established health consequences.

The beef you eat and the milk you drink: Many farm-raised cattle are injected with artificial growth-promoting hormones such as oestradiol, progesterone, testosterone, zeranol, trenbolone and melengestrol to promote rapid meat production. Recombinant bovine growth hormone (rBGH) is a genetically-engineered synthetic hormone used to increase milk production in cattle, which then communicates to your liver to increase the production of Insulin-Like Growth Factor-1 (IGF-1). Although no systemic studies have directly researched the health effects of these hormones in the body, associations with DNA damage, infertility, premature puberty and risk for breast, prostate, colon, and lung cancer have been found retrospectively^1,2.
Ultra-processed foods: How often are you eating chips, bagels, pizza, soda, and other highly-processed food items without thinking twice about how they are manufactured? Based on the NOVA system classification, ultra-processed foods go beyond the addition of salt, sweeteners, or fat and include artificial flavors and preservatives that increase the shelf-life in your kitchen cupboards, preserve the texture of foods and increase their palatability to leave you craving for more. More and more studies are being published linking these foods to heart disease, heart attacks, and death from cardiac causes³.
Aspirin, Tylenol, and Ibuprofen: You likely reach for these common analgesics in your cabinet when you have pain, inflammation, or fever to alleviate the symptoms you are suffering from. However, there are risks and rare side effects associated with taking these drugs that include serious allergic reactions, kidney damage, bleeding, heart attacks, and stroke⁴. This is not meant to scare you into never taking these medications but to bring to light the many decisions we make that are more likely to benefit us rather than harm us.
Air pollution: How often do you grab your smartphone to check the air quality for the day? If the quality is less than ideal, how often does that impact whether you go outside? Poor air quality has been associated with heart disease, long-term respiratory problems, stroke, and low life-expectancy^5,6. However, the benefits of staying physically active outside, experiencing life events, socializing to improve mental health, and anything else that provides meaning in our lives by being outside likely outweight many of these risks.
The sun: Everyday, UV radiation from the sun and our atmosphere produce reactive oxygen species that cause direct DNA damage. This can lead to skin aging, skin cancer, and eye damage. Despite these risks, the benefits the sun provides to our planet and existence outweigh the risk and allow us to appreciate the positives⁷.

Every decision we make involves a conscious or subconscious risk assessment rooted in our values. As physicians, we are committed to providing medical advice based on whether the benefits outweigh the risks for our patients. While I can and will validate your concerns and fears, I hope that in the future you might consider seeing the forest for the trees.

References:

https://www.jswconline.org/content/68/4/325
http://ifrj.upm.edu.my/25%20(01)%202018/(1).pdf
https://www.jacc.org/doi/10.1016/j.jacc.2021.01.047
https://link.springer.com/article/10.1007/s12325-019-01144-9
https://link.springer.com/content/pdf/10.5487/TR.2014.30.2.071.pdf
https://www.sciencedirect.com/science/article/pii/S1875213617301304
https://link.springer.com/article/10.1007/s13273-017-0002-0

It is Time to Try Something New!

March 4, 2022February 22, 2022 Bhavya Varma, MD

The internet has revolutionized medical education. Going through medical school– the resources are endless! It’s fun trying to figure out what’s best for your learning style but given the sheer volume of all the great content it can also be overwhelming.

Podcasts became one of my favorite ways to learn while in medical school. The internist in me craves the part of the day when I can listen to the attending think out loud. It’s all about understanding an expert’s thought process so you can begin to develop your own when it comes to cool and complex pathophysiology. Podcasts allow accessibility on demand. What a gift – and there are so many fantastic medical podcasts in production today. I couldn’t be more thankful to the doctors and educators who put their time and energy into providing free and fantastic education for so many of us.

As my career develops and I focus my interests, CardioNerds has become one of my of favorites. They take this concept of listening to experts think out loud to another level. I recently listened to a “CardioNerds Rounds” episode which involved an expert, Dr. Kittleson, sharing her thoughts on challenging hypertrophic cardiomyopathy cases. It was riveting in the way that she laid out a wonderful foundation for those still learning and at the same time discussed nuanced management that doesn’t always follow a script. Now that is cool.

Another aspect of the CardioNerds platform that has been admittedly less approachable for me is the Twitter Journal Club. As a resident, learning about cutting edge research and practice changing guidelines is not only rewarding because it delights my academic curiosity but its crucial in improving patient care. With an unending repository of gigantic new trials that continues to grow every single day, it is difficult to decipher these alone. That it where #CardsJC¹ (the CardioNerds Twitter journal club) is magic.

I strongly believe the power of medicine specialties lies within the team aspect. I know our reputation has humorously involved discussing hyponatremia for an hour on rounds, but truly when the whole team is invested in discussing something new or controversial it is so much fun! That is what #CardsJC can provide, experts dissecting and explaining the meaning of a trial so it’s not just taken at face value but what it means for advancing patient care. This is how you learn in medicine, not just by memorizing, but by deepening your understanding; wrapping your head around how something came to be and where it is going. As a second year resident, I found the best teachers are usually masters of their content. This is especially highlighted when your own interns and med students want to learn more about a topic – I’m usually most successful when I take the time to prepare and be intentional.

#CardsJC gives us access to this. CardioNerds is a multimodality digital education platform with a mission to democratize cardiovascular education^1,2. They held their first Twitter journal club about a year ago in February 2021. They are thoughtful in involving leading experts, trial authors, guidelines authors, and society leaders in the conversation². Twitter’s unique platform allows for this innovative new approach to journal club. Additionally, for young learners it can be intimidating to speak up in traditional journal club settings where you barely grasp the basics much less feel comfortable challenging methodology or ideas. Twitter once again allows for anyone to engage on their own terms without the terror of having to raise your hand in a room full of highly accomplished people – we’ve all been there!

In addition to the nuanced conversations, #CardsJC comes with detailed trail summaries, infographics, and carefully crafted tweets¹. This is an effective, practical, and revolutionary way for busy participants in all stages of their careers to engage with new data and integrate this into their practice. It’s a way for us to engage in rich discussion with those who may not have been accessible to us in the past. It’s also a way to create great archives of information you can refer to later, especially the trial summaries.

If you were like me and hesitant to engage with this platform in the past because it was unfamiliar – there’s even a video tutorial¹! I really enjoyed this because it makes the process simple and approachable. This main #CardsJC page also includes trial summaries from past journal club discussions. Overall, I highly recommend joining the next #CardsJC on March 29^th to get your feet wet! It’s sure to be a fantastic discussion about an important upcoming topic – but I won’t give away any clues just yet.

References:

Cardionerds Journal Club – join the conversation on #cardiotwitter! Cardionerds. (2022, January 18). https://www.cardionerds.com/cardsjc/
Dugan, E., Ferraro, R., Hamo, C., Ambinder, D., & Goyal, A. (2021). The cardionerds #cardsjc: How twitter journal clubs elevate the scientific discourse. Journal of Cardiac Failure, 27(9), 1034–1036. https://doi.org/10.1016/j.cardfail.2021.04.012

Vascular Discovery 2022: From Genes to Medicine

March 3, 2022February 22, 2022 Huan Wang, PhD

Have you been lingering on what else is going on within the field of atherosclerosis research after this year’s Scientific Sessions in American Heart Association? You might want to check out Vascular Discovery 2022, a 2 ½-day meeting, which is sponsored by the Council on Arteriosclerosis, Thrombosis and Vascular Biology, the Peripheral Vascular Disease Council, and the Council on Genomic and Precision Medicine, in cooperation with and the Society for Vascular Surgery’s Vascular Research Initiatives Conference (Flyer on the right).

What is the conference about?

The primary goal of the Vascular Discovery: From Genes to Medicine Scientific Sessions is to provide a forum for the timely exchange of information about new and emerging scientific research in lipids and lipoproteins, arteriosclerosis, thrombosis, vascular biology, genomics, precision medicine, peripheral vascular disease, and vascular surgery.

One of the long-standing objectives of this conference is to provide a unique platform for colleagues to build valuable networks, establish potential collaborations and promote early career scientists via providing role model inspirations and mentorship opportunities. The advantages of direct social interactions are indisputable, especially when it comes to build meaningful relationships. This year’s Vascular Discovery will be held in-person in Seattle. It will bring colleagues from worldwide, share groundbreaking science and bridge different disciplines in a classic old fashion way.

Who should attend?

This event will appeal to scientists and clinicians in cardiovascular medicine, cardiovascular research, thrombosis research, clinical cardiology, molecular/cellular biology, vascular biology, vascular medicine, vascular surgery, endocrinology, genetics, functional genomics, hematology, immunology, nutrition, and physiology.

Past highlights and feature events

While the planning committee is finalizing the abstracts and awardees, we can take a glimpse of what happened in 2021, which will shed some lights into the 2022 scientistic sessions. Vascular Discovery presented a virtual experience to the attendees in 2021, because of COVID pandemics. Since COVID has been the primary attention in public and scientific communities the past couple years, one of the important focuses of Vascular Discovery 2021 is on understanding how COVID-19 affects vascular systems, to identify who and when to treat patients in vascular research and clinical trials. Other important discussions are on identifying new approaches to understand the pathophysiology of atherosclerosis via risk factor identifications, and a distinguished lecture was presented by Marlene Rabinovitch, M.D. on multiple approaches of identifying a therapeutic target for treating pulmonary hypertension. More highlights are shown in the American Heart Association website¹.

Are you excited about attending this year’s in-person Vascular Discovery: from Genes to Medicine Scientific Sessions in Seattle? Stay tuned on the latest programming of 2022, which hopefully will be finalized and released in early March.

Registration for the Vascular Discovery Conference is now open. Early Bird pricing closes on 3/31, and Advance pricing opens on 4/1. Register now for the best price!

REFERENCE

1. American Heart Association. Science News 2021. https://professional.heart.org/en/meetings/vascular-discovery-from-genes

Insights About COVID-19 Health Outcomes in Smokers from Hospital Records

March 2, 2022February 21, 2022 Jessica Monterrosa Mena

Early in the COVID-19 pandemic, clinicians noticed that some patients with pre-existing medical conditions were at higher risk of severe illness and death. Since then, many observational studies confirmed that people with diabetes, asthma, or cardiovascular disease had a substantially higher risk of COVID-19-related complications and death^1,2. Such studies typically use hospital patient records to study relationships between individual risk factors, like age and sex, and long-term health outcomes. However, studies using hospital record data revealed that smokers may be underrepresented among patients with COVID-19, as highlighted by a recent review study of publications reporting smoking prevalence and clinical outcomes in patients diagnosed with COVID-19³. The review highlights that only a single study out of 15 research articles examined had reported a prevalence of smokers among patients with COVID-19 that resembles the smoking prevalence of the general population. Such findings, raises the question of whether a smoker’s paradox exists with the COVID-19 pandemic. The smoker’s paradox refers to the observational phenomenon of smokers exhibiting improved prognosis and decreased short-term mortality, following cardiovascular events. This idea has been mostly debunked now as a bias in the analysis of observational data and smoking is not considered to be a causative factor that improves health outcomes⁴. So, what considerations should be taken when interpreting health records of patients in order understand whether smokers fare worse COVID-19 outcomes than non-smokers?

Questioning Data Quality and Biases in Patient Record Data

Smoking is associated with many immediate and long-term health consequences, and initiates disease promoting mechanism in cardiopulmonary tissues. A low representation of smokers in hospitalized COVID-19 patients may be due to biases in patient record data collection. A small percentage of people who perceive stigma associated with smoker status may actually conceal smoker status during a primary care visit⁵. Furthermore, smoker screening often does not include questions about smokeless tobacco, electronic cigarette use, and second-hand smoke use, despite the rise in popularity in electronic nicotine delivery systems and cigarette alternatives⁶. Standardization and improved tobacco-related electronic health record questionnaires may begin to address the question of how much tobacco smoke a person is exposed to by including questions that cover sources of exposure, quantity of use, and duration of exposure. Collecting patient data that covers a larger range of exposure possibilities including having someone else in the home that smokers, or individual behaviors of switching from traditional cigarettes to electronic cigarettes, smoking cessation patterns, and years of use may provide better insight into how smoking behaviors influence health outcomes. In the context of the COVID-19 pandemic, smokers’ status is difficult to ascertain in patients who are intubated, sedated, and unresponsive. Closely tracking individual smoker status over time is helpful in those situations when a patient’s care plan should include tobacco withdrawal symptom management.

Smoking directly influences cardiovascular and respiratory health outcomes and using hospital data to derive associations with COVID-19 health outcomes is prone to confounding bias, reverse causation, and inappropriate adjustments in analysis models. In the future, it be possible to use human biomarkers to uncover the specific health effects from smoking. This might include correlating urinary levels of nicotine and cotinine to understand the burden of different tobacco products. For now, research using animal models to assess the health effects of traditional smoking and electronic cigarettes provide insight into the short- and long-term consequences of smoking and elucidates the biochemical processes that exacerbate disease including tissue repair processes, inflammation, and oxidative stress. Understanding the mechanistic processes involved in the exacerbation of COVID-19 disease among smokers may ultimately help identify biomarkers of disease progression and pharmacological treatments for vulnerable populations.

References:

Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-436. doi:1038/s41586-020-2521-4
Why lighting up and COVID-19 don’t mix. American Heart Association News. https://www.heart.org/en/news/2020/05/05/why-lighting-up-and-covid-19-dont-mix#:~:text=Studies%20from%20Wuhan%2C%20China%2C%20where,%2C%20compared%20to%20non%2Dsmokers.
Usman MS, Siddiqi TJ, Khan MS, et al. Is there a smoker’s paradox in COVID-19? BMJ EBM. 2021;26(6):279-284. doi:1136/bmjebm-2020-111492
Doi SA, Islam N, Sulaiman K, et al. Demystifying Smoker’s Paradox: A Propensity Score–Weighted Analysis in Patients Hospitalized With Acute Heart Failure. JAHA. 2019;8(23). https://www.ahajournals.org/doi/10.1161/JAHA.119.013056
Stuber J, Galea S. Who conceals their smoking status from their health care provider? Nicotine & Tobacco Research. 2009;11(3):303-307. doi:1093/ntr/ntn024
LeLaurin JH, Theis RP, Thompson LA, et al. Tobacco-Related Counseling and Documentation in Adolescent Primary Care Practice: Challenges and Opportunities. Nicotine & Tobacco Research. 2020;22(6):1023-1029. doi:1093/ntr/ntz076

Medical Imaging – the Window to the Brain of Moyamoya Disease Patients

February 28, 2022February 14, 2022 Moss Zhao, PhD

In our previous blog, we discussed Moyamoya disease – a cerebrovascular disorder that affects the blood vessels in the brain and disproportionately affects women and Asians. It often begins in childhood and causes the patient to have a high risk of stroke. In this blog, we will discuss the process of how Moyamoya disease is diagnosed using medical imaging.

When a patient presents symptoms of Moyamoya disease such as blurred vision, muscle twitching, and/or weakness of one side of the body, a physician may order an imaging exam including computerized tomography (CT), magnetic resonance imaging (MRI), or digital subtraction angiography (DSA). These scans can show the structure and functions of the brain and whether the blood vessels are occluded (blocked). The scan often takes place for about 30 minutes and the side effects are negligible. A radiologist would interpret the scans and produce a report about the findings based on the images. Depending on the type of the scan performed, this report often includes information about the structure and functions of the patient’s brain, whether there are lesions, the blood flow in the brain, and the blood vessels in the brain and neck.

Doctors can also order an advanced MRI procedure whereby the patient is given a drug during the MRI exam. Typically, the drug is injected intravenously by the attending MR technologist during the scan. This drug is known as acetazolamide or Diamox, and it is often used to treat altitude sickness. Scientists found that acetazolamide can also increase the blood flow in the brain for a short period of time without harming the patient. As we mentioned in the previous blog, Moyamoya patients often have a high risk for stroke during stressful conditions. By giving the patient acetazolamide during an MRI scan, doctors can create a temporary and artificial stressful condition to determine if the patient has a high risk for stroke. The effect of acetazolamide should subside after a few hours of the MRI exam. Recently, researchers at Stanford University demonstrated this technique to identify high-risk Moyamoya patients.

Image source: Stroke

References:

https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.117.017773

The Researcher’s Ultimate Toolkit: The PPI network Passion, Perseverance, and Interaction.

February 25, 2022February 22, 2022 Melody Chemaly, PhD

I had the pleasure of having a one-on-one virtual meet-up with Mabruka Alfaidi MD, PhD who won the ATVB Investigator in Training Award Competition during last year’s Vascular Discovery 2021 meeting based on her fascinating work on endothelial cells and IL-1b signaling pathway as well as her active involvement with the research community. We discussed her career path and her future projects which we couldn’t do without also going over the many hurdles that come our way as researchers. I decided to summarize the main themes that we tackled in a researcher’s toolkit which encompasses key ingredients to sustain a career in research: The PPI network.

Passion: Follow your passion, but it’s ok to be unsure

Mabruka Alfaidi is a postdoc at Louisiana State University and is currently an instructor seeking her research independence. For Mabruka, her passion for research started when she was a clinical cardiologist and when she realized that one needed to do more to save patients’ lives. Her PhD at the University of Sheffield in the UK opened her eyes to the field of IL1-b signaling in endothelial cells which further developed into her research passion and the basis on which she would like to build her future research career. Research without passion is unsustainable. Passion is the fuel which will motivate us to wake up in the morning (or in the night) and check the latest research, be inspired by the newest methods and design novel hypotheses. However, it is ok to be unsure sometimes when trying to figure out our next step; do we want to stay in academia, or should we venture into setting up this start-up that we always dreamed of? Nothing is really set in stone because research, just like our passion for it, is a dynamic process and it evolves.

Perseverance: It’s ok to fail

A career in basic research is impossible without facing failures and hardships. For Mabruka who started her research path with a medical background, failure, which is assimilated to losing a person’s life in medical practice, was not an option. However, life as a basic researcher is surrounded by failures. We have all struggled with experiments not working, manuscripts getting rejected, grant applications not receiving any interest and the list goes on. So, becoming a basic researcher coming from a medical background is definitely an adjustment. In those moments where doubt creeps into our heads and our confidence and self-esteem is at its lowest, it is important to be surrounded by the right people and inspiring mentors to give us this moral boost that we need to persevere and remind us that it is ok to fail.

Interaction: Network and share your experience, you are not alone

It is common for researchers to feel isolated in their own niche of research and drown in it. However, sharing one’s experience with the research community is important to learn from others and be presented with new opportunities. Mabruka’s experience with the AHA community helped in her career development as the organization provides funding opportunities for early career researchers as well as those seeking independence and is an important platform where basic and clinical researchers can communicate and find common ground. However, Mabruka’s involvement with AHA and other research communities is because she feels that it is important for a researcher to always ‘give back’ to the community as a way to acknowledge the help and contribution they received and carry on the flame.

Combining CAR-T and mRNA Therapeutics to Cure Heart Failure

February 23, 2022February 14, 2022 Khairunnisa Semesta, MA

Heart failure is the leading cause of death in the Western world, causing more than 300,000 deaths per year. Heart failure is also a source of significant economic burden, costing the American healthcare system more than 30 billion dollars in 2012.[i] Cardiac fibrosis is central to the pathology of heart failure. Cardiac fibroblasts are activated in response to injuries. However, when activated fibroblasts fail to quiesce and continue secreting extracellular matrix, cardiac fibrosis occurs, leading to scarring of heart tissues. Ultimately, cardiac fibrosis can lead to fatal heart failure. Fibrotic diseases, including lung and cardiac fibrosis, cause more than 800,000 deaths worldwide per year.[ii]

Researchers from the laboratory of Dr. Jonathan Epstein in the University of Pennsylvania recently showed that mRNA therapeutics can be used to address cardiac fibrosis.[iii] The researchers delivered a modified mRNA coated with T-cell targeting lipid nanoparticles. The mRNA encodes for a chimeric antigen receptor against FAP, a specific protein expressed by activated fibroblasts. This allows for the generation of transient chimeric antigen receptor T (CAR-T) cells that recognize fibrotic cardiac cells.

Successfully delivered, the mRNA was able to reprogram T cells to specifically recognize and eliminate activated fibroblasts. In a mouse model of heart failure, the engineered CAR T cells were able to resolve cardiac fibrosis, restructuring the heart and improving heart function after injury. Unlike ex vivo CAR-T cells generation, this method allowed the generation of CAR T cells entirely in the human body. In addition, these engineered CAR T cells are transient, therefore not compromising the heart’s ability to resolve future injuries through fibroblast activation.

With the recent advances of the COVID-19 vaccines, the use of mRNA therapeutics in other diseases is gaining traction. The possibility of eliminating the disease burden of cardiac fibrosis using mRNA therapeutics is extremely attractive, as it has the potential to reverse cardiac fibrosis and restore heart function. This presents a significant addition to existing antifibrotic agents that only limit or slow down fibrosis progression. This first proof-of-concept study opens a new avenue to optimize the strategy of combining mRNA therapeutics and CAR-T technology to address cardiac fibrosis and fibrotic diseases in general.

References:

[i] Virani, S. S. et al. (2021) Circulation 143: e254–e743

[ii] Hinderer, S. and Schenke-Layland, K. (2019) Advanced Drug Delivery Reviews 146: 77-82

[iii] Rurik, J. et al. (2022) Science 375.6576: 91-96

Women in Electrophysiology

February 21, 2022February 14, 2022 Lina Ya'qoub, MD

While I was chatting with a few fellows in our hospital hallway, I met one of the fellows who was very interested in electrophysiology (EP). We had a very interesting chat about her application and future career forward. In this blog, I summarize my chat with Jasneet Devgun, an aspiring electrophysiologist.

Question: Hi Jasneet, great to have you here! Let’s start with this question: When and how did you know you love EP?

Answer: EP is something I never really thought of pursuing initially. In fact, I was interested in interventional cardiology since my second year of medical school. It was not until I met an electrophysiologist at the University of Chicago during my third year of medical school that I thought of EP as a possible future career. He was so excited to show me the world of EP and frequently took me to the lab to see EP in action. I still remember the day he said, “we need more women in EP…you should consider it.” From then on, my curiosity grew. I found myself drawn to the lab, scrubbing in on cases in residency and fellowship. The unique therapeutics, cutting-edge procedures and technology, intellectual and logical nature of EP, alongside very memorable and rewarding encounters with patients and wonderful attendings, made me realized that EP was the right field for me.

Question: This is great!! What are your thoughts about women in EP?

Answer: Last year, Dr. Kamala Tamirisa wrote a very thoughtful piece for EP Lab Digest on the EP fellow shortage.¹ At the time, the National Resident Matching Program (NRMP) demonstrated that approximately 40% of 130 EP fellowship positions in the US were unfilled.²In 2021, that number drastically declined to 4%. Despite clear rising interest in EP, there remains a paucity of women in the field. The American Board of Internal Medicine (ABIM) reported that women comprised only 10% of first year EP fellows, while remaining steady at this rate for the past 10 years.³

The paucity of women pursing EP is a multi-faceted issue. A recent survey of cardiology fellows-in-training published in the Journal of American College of Cardiology showed that the most significant reasons women did not choose EP were greater interest in another field, radiation concerns, lack of female role models, a perceived “old boys’ club” culture, and discrimination/harassment concerns.⁴ Another reason was length of training. Reasons why women did choose EP were positive mentorship, unique features about the specialty, expertise, and the presence of a female role model, the latter being the major influencer.

These results are not surprising, but there are ways we can tackle the question at hand.

Question: Absolutely!! And this brings up the importance of mentorship, can you share your experience with that?

Answer: I cannot stress enough the value of a good mentor. A good mentor inspires and cultivates the foundations of turning one’s future into reality. This was personally a huge factor for me; I did not know anything about, let alone consider, EP until I met electrophysiologists who had a genuine interest in my career development. Interestingly, none of them were female. Our male colleagues can be some of our biggest advocates. I certainly see how a female role model is uniquely relatable and valuable. However, the gap will remain until more females in EP exist. That said, networking with female electrophysiologists through existing organizations, as well as creating outreach/interest groups in-person and on social media to involve residents, medical students, and even undergraduate students, would be very effective.

Question: What advice do you have for fellows who do not know much about EP or are not sure if they would want to pursue it? What are some possible barriers to developing interest?

Answer: Exposure is key! Many trainees do not have much exposure to EP, and therefore may not know enough to develop an interest for it. Fellows should be aware of the distinctive benefits and exciting features unique to EP, which can only be achieved by increasing their time with electrophysiologists and the EP lab. This can also dispel concerns about radiation safety. For example, female cardiology fellows concerned about radiation in the survey may not know about the use of 3D mapping systems and multi-modality imaging, affording “low-fluoro” or “fluoro-less” cases and reduction in procedure times. Moreover, the development of robotically assisted procedures has provided an avenue to reduce occupational hazards.
I was fortunate that my residency program offered an EP elective, where I met electrophysiologists who were excited to show me their world. A structured elective early in residency and more electives for medical students, with some exposure to the lab, may help bridge the gap and channel early interest. The earlier it is, the better, since interests develop quickly (as did mine!).

Question: What are your thoughts on the length of training and how this may be impacting fellows’ wellness and career decisions?

Answer: Length of training is an important issue.^1,4 This time overlaps with childbearing years and critical family development. Fellows, both male and female, should not have to feel like they must choose one over the other. There must be a genuine culture of promoting work-life balance during the long years of training. Fellows are also consequently faced with prolonged financial strains from student loan debt. These are things that fellows consider when deciding to pursue another fellowship. As medicine progresses towards a milieu of sub-specialties requiring ever-more training, the training structure must be modernized to optimize the workforce. Unfortunately, many people, including female fellows, may be missing out on great sub-specialties like EP because of these issues. Some have proposed modifying the last 6 months of cardiology fellowship as the beginning of CCEP, which is a great short-term goal.¹ A “fast-track” program in fellowship that may even extend into residency may be a proposition for much later in the future. These changes can make a major difference in fellows’ career decisions, health, and well-being.

Despite the paucity of women in EP, I am positive that the great strengths of this field will surpass any barriers to recruiting them. Building exposure early, having more visible role models and mentors, modification of the training structure, and many other solutions previously stated will allow for tremendous progress. Even simple interventions can make leaps and bounds in bringing more women into the wonderful world of electrophysiology.

I would like to thank Jasneet Devgun, DO, who is currently a general cardiology fellow at Henry Ford Hospital, and an aspiring electrophysiologist, for sharing her experience and thoughts with us. A special thank you goes to Dr. Judith Mackall and Dr. Cristina Tita who helped in writing this blog.

References:

Tamarisa, K. The Importance of Choosing Cardiac Electrophysiology as a Career: Thoughts on the EP Fellow Shortage. EP Lab Digest. Available at https://www.hmpgloballearningnetwork.com/site/eplab/importance-choosing-cardiac-electrophysiology-career-thoughts-ep-fellow-shortage. Accessed October 9, 2021.

Fellowship Match Data and Reports. National Resident Matching Program. Available at http://www.nrmp.org/fellowship-match-data/. Accessed October 9, 2021.
Percentage of First-Year Fellows by Gender and Type of Medical School Attended. Available at https://www.abim.org/about/statistics-data/resident-fellow-workforce-data/first-year-fellows-by-gender-type-of-medical-school-attended.aspx. Accessed October 9, 2021.

Abdulsalam N, Gillis AM, Rzeszut AK, Yong CM, Duvernoy CS, Langan MN, West K, Velagapudi P, Killic S, O’Leary EL. Gender Differences in the Pursuit of Cardiac Electrophysiology Training in North America. J Am Coll Cardiol. 2021 Aug 31;78(9):898-909. doi: 10.1016/j.jacc.2021.06.033. PMID: 34446162.