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PET or MRI, that is the question – Part 2

In our previous blogs, we discussed ASL MRI to image abnormal blood vessels in Moyamoya patients. We looked at a study that compared MRI and PET images of normal and healthy people. In this blog, we will look at the application of ASL MRI on adult Moyamoya patients.

According to the latest study by Dr. Moss Zhao (AHA Postdoctoral Fellow, 2021), ASL MRI can detect impaired blood flow and circulation in Moyamoya patients without any radiation or contrast agents.

In this study, Dr. Zhao’s team enrolled nearly 30 adult Moyamoya patients without acute stroke or tissue infarcts in the brain. They scanned the brain of these patients using the advanced ASL MRI technique (multi-delay ASL) that were tested successfully on normal and healthy people before. Similar to the study designed in the previous blog, Dr. Zhao’s team collected both ASL and PET images from the Moyamoya patients at the same time before these patients underwent their bypass surgery. The results from this study were convincing that ASL can replace PET to characterize the pathophysiology of Moyamoya disease patients. The image in this blog shows the vessel occlusion and its impact on blood flow in a Moyamoya patient.

Another advantage of ASL is the elimination of contrast agents. In many MRI exams, patients need to receive a contrast agent (such as gadolinium) to enhance the image quality. However, the contrast agent can cause side effects and deposit in the brain. Although there is no evidence suggesting its impact on health, we should minimize the use of these contrast agents. In the same study, Dr. Zhao’s team also demonstrated that the advanced ASL can create images without contrast agents and that doctors favored the new ASL technique over the conventional contrast-based imaging method.

Taken together, ASL MRI will become more accessible to radiologists to diagnose Moyamoya disease without causing side effects to patients. The technique will allow safe, affordable, and fast for imaging to identify patients with a higher risk for stroke.

Image source: JCBFM

 

REFERENCE

https://doi.org/10.1177/0271678X221083471

 

“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.”

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The Power of Mentorship

As many of us are finalizing our application for fellowship this summer, it’s also a wonderful time to reflect on the journeys that brought us here. It’s no small feat to complete undergraduate training, medical school, and internal medicine residency and have all of that hard work culminate in this application for cardiovascular fellowship training. I’m excited and often blown away by the creativity and successes of my fellow applicants.

One aspect of this journey I’ve reflected on most deeply has been mentorship. I cannot state how important it is to find the right mentors in a process like this one. There is no one-size-fits-all, as we are all unique personalities with individual interests and aspirations. For those hoping to apply in the future, what I found to be most important is finding people you want to model yourself after.

A difficult part of this process can be the first step! How do you approach those you might be interested in working with? I met my research mentor prior to starting my residency, via Twitter. I was looking up people involved in women’s cardiovascular disease at my new institution, and a few names quickly rose on the list. My mentor had posted on Twitter recently about the importance of women in cardiology and creating an inclusive and equitable environment moving forward. Her studies span women’s cardiovascular disease but also advocate for women in research and the academic sphere. I knew this was someone I wanted to work with. I messaged her on Twitter and was met with the warmest welcome. I share this story to encourage young trainees to be proactive in searching for mentors. Take that first step, send that email, and explain why you want to work with them. My research mentor is a fierce advocate for young women trainees. At a recent CV conference in Chicago, I experienced first-hand how she uplifted medical students, residents, postdocs and made us all feel like we belonged in this space. I’m certainly grateful for trailblazers like her who are changing the face of cardiology.

You will also find wonderful mentors via clinical rotations! As an intern in the CCU, I was blown away by our CCU director. He is the kind of teacher you want to show up for. It’s not out of fear but out of respect that you want to be overly prepared for rounds in the morning, so you don’t disappoint. Together, we talked to patients about their pacemaker settings and their heart transplant status, and I found my joy for interpreting swan numbers every morning. Once again, I found someone I wanted to be like one day. He brought so much energy and enthusiasm that the whole team was excited to learn. He created a learning environment that encouraged us to ask questions and never be afraid. Most of all, he reminded us that everything is in the service of our patients. You want to seek out those invested in your growth as a trainee and those who excite you about a future in cardiovascular medicine.

Each mentor can bring something very different in shaping you and influencing the physician you will become one day. I encourage all young trainees and medical students to find people in their field who keep them excited, humble, and always striving for growth. Don’t be afraid to ask these teachers about their journeys and advice regarding your own career trajectories. In my experience, they are usually more than happy to help. From a practical standpoint, talk to residents and fellows in your program about who may be a good fit based on your interests and goals. Medical training is a long journey with many phases, and I have found most of us are very happy to pay it forward.

There have been countless mentors who have brought me to this point and I could write a novel about each of them and what they mean to me. For now I will say, if you are early in your career don’t underestimate the importance and impact of finding the right mentors. Doing so intentionally and thoughtfully both as a mentor and mentee can create environments that encourage people to reach their full potential. If you’re a young trainee reading this, be mindful about finding your village. They will shape who you become one day, don’t be afraid to reach out and introduce yourselves. You can find mentors in non-traditional settings as well in the era of digital education and MedTwitter. Create a network, talk to people at large conferences, and reach out to those you have worked with clinically. If you’re in the position to uplift others, investing in those who will come after you means everything to us. We are so grateful for all you 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 health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”

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The controversy over alcohol consumption: Is it good or bad for your heart?

If you go to a party or a professional event, you won’t be surprised to find that alcoholic beverages are served. In fact, in most cases, it’s even expected. Alcohol consumption has been present throughout human history. So do its effects. Excessive drinking has been linked to many health risks, including high blood pressure, heart diseases, stroke, liver diseases, and digestive problems. However, the health effects of light-to-moderate drinking are still in dispute (1). Early evidence showed that light-to-moderate drinking is associated with beneficial effects such as reductions in coronary artery diseases and even in total mortality. This view has been challenged by a few recently published epidemiological studies, which show no direct relationship between the beneficial effects on the heart and light-to-moderate drinking (2).

What is light/moderate drinking?

According to National Institute on Alcohol Abuse & Alcoholism, moderate drinking is up to four alcoholic drinks for men and three for women in any single day and a maximum of 14 drinks for men and 7 drinks for women per week. Below that range would be considered light drinking.

Why is there a discrepancy in health risks reports on alcohol consumption?

The obvious:

Confounding factors such as social-economic status, age, genetics, ethnicities, behavior and types of alcoholic beverages play big roles in influencing health effects. It’s not hard to imagine that a wealthy family has more medical resources and more options of choosing a healthy lifestyle, which has lower risks of cardiovascular diseases compared to a low social-economic status family that even consumes the same amount of alcohol. The alcohol metabolism rate differs in different age groups and different populations. The certain population lacks an enzyme, alcohol dehydrogenase, which metabolizes alcohol, that has adverse health effects when drinking alcohol. These confounding factors are important when conducting an epidemiology study. Not all alcoholic drinks are created equal. Bioactive phytochemicals, for example, polyphenols have beneficial effects which can be found in wines. Cocktails usually contain a large amount of sugar, and high sugar consumption are linked to many cardiovascular disorders. It’s hard to tease out the causal effects of light-to-moderate alcohol consumption and the health effects. Moreover, most of the reported works of literature are observational, which leads to more complications when trying to interpret the data.

The less obvious:

Epidemiological study design has evolved rapidly in recent decades. Early studies were focused on interpreting results from limited resources. The lack of enough participants and missing specific details make it impossible to make a causal connection between alcohol consumption and health risks. In 2007, researchers started to encourage epidemiological studies to use large, prospective, and randomized trials when trying to understand the health effects of drinking (3). A recent review just published in Circulation: Heart failure questioned the relationship between alcohol intake and cardiomyopathy and heart failure (4). After analyzing current evidence, they suggest that there is no consensus on the absolute amount alcohol intake which causes cardiomyopathy and heart failure. Another group showed that low alcohol intake has no health benefits, and moderate alcohol intake is associated with adverse effects in heart (5).

To drink or not to drink. There is no one-size-fits-all solution. The jury is still out when it comes to the health effects of light-to-moderate drinking. Monitor your health and consult with your doctor regularly. If it’s not good for you, your body will tell.

REFERENCE

  1. Piano, M. R. (2017). Alcohol’s Effects on the Cardiovascular System.Alcohol Research : Current Reviews38(2), 219–241.
  2. Biddinger, K. J., Emdin, C. A., Haas, M. E., Wang, M., Hindy, G., Ellinor, P. T., Kathiresan, S., Khera, A. v, & Aragam, K. G. (2022). Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease.JAMA Network Open5(3), e223849–e223849.
  3. Kloner, R. A., & Rezkalla, S. H. (2007). To Drink or Not to Drink? That Is the Question.Circulation116(11), 1306–1317.
  4. Andersson, C., Schou, M., Gustafsson, F., & Torp-Pedersen, C. (2022). Alcohol Intake in Patients With Cardiomyopathy and Heart Failure: Consensus and Controversy.Circulation: Heart Failure0(0), 10.1161/CIRCHEARTFAILURE.121.009459.
  5. The abstract ‘Moderate alcohol consumption is associated with progression of left ventricular dysfunction in a European stage B heart failure population’ will be presented during the session ‘Heart failure is a complex syndrome: look at comorbidities’ which takes place on 22 May at 09:40 CEST at Moderated ePoster 1.

“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.”

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My First Year As An Attending – What I have learned

After many years of training, it finally happened, I was going to be an attending. The goal we all strive for – to take the training wheels off, practice what we learned, and provide the best care possible for our patients. I spent months leading up to my first week on service incredibly nervous and found myself reviewing guidelines, trials, and any other resource to help me succeed – safe to say, I was psyching myself into a frenzy.

Like many of us, the fear of failure is an incredibly motivating factor but perhaps not the healthiest mindset. I’d like to share my journey as a first-year attending and what I learned in hopes of helping others who are finally taking off the training wheels.

Day 1 as attending, celebrating great news our patient was undergoing heart transplant.

1. Your department wants you to be successful. It may feel like you are alone as an attending, but your department invested a lot of time and resources for you to join. They want you to succeed and encourage open lines of communication. The senior members in both my departments (cardiology and critical care) expected me to call them when I was struggling with a challenging case, needed clarity on how to navigate the new system I was working in, and to touch base on how I was doing. I have called my colleagues on the weekends and at odd hours to ensure I was providing the best care for my patients – and the best part, they did not once make me feel inferior or as if I was doing a bad job.

2. Push your socializing boundaries. When I started working for UPMC, I only knew the handful of people who interviewed me. Many of my colleagues knew who I was through the continued updates from our division leadership regarding new hires but to me, everyone was a stranger. The best way I can describe it is as a year of continued blind-dating. I would meet faculty members, make small talk, and then move on.

I, therefore, made it a mission to get to know as many people as possible. I would introduce myself to all of the nursing staff in the mornings when I would see patients. This gave me a chance to get to know my CICU/CTICU team and get updates on the patients. When I would meet other attendings (in cardiology and critical care), I would introduce myself and get their phone number. I took the same approach for attendings who were consulting on my patients so I could continue to develop relationships across the health care system.

I’m fortunately a very social person, so this was not a terribly big challenge but if you are a bit shyer, this may very well feel uncomfortable and awkward. Keep in mind, that your colleagues want to get to know you (as you are the newest hire) but you have to get to know an entire division’s worth of faculty. Plus, if you throw in the trainees it becomes an even bigger task.

Supporting Go Red For Women with the entire CTICU Team

3. Don’t be afraid to ask for help. In order to be successful, don’t be afraid to ask for help, whether that is related to patient or personal care. Being a new attending has numerous challenges but asking for help isn’t one of them. I remember a difficult case being evaluated amongst our cardiogenic shock team to discuss the possibility of placing a patient on ECMO. I wasn’t sure the best course of action as I was the attending in the CTICU that week and my input would be heavily weighed. I immediately reached out to our CTICU Medical Director to hop on the call. He was able to give his insight on the case, which helped us determine a better clinical course. I was able to debrief with him afterward and learned for the next time I would encounter a similar situation.

4. Don’t forget your past mentors. Many of us will start working as hospitals we have never stepped foot in. Our past relationships are of incredible value. I still text and call my mentors for advice. They are a great objective 3rd party to speak to.

5. Enjoy the process. Being an attending is hard but remember the years of training you have completed getting to this point. We became physicians to accomplish a variety of goals (research, clinical care, etc) and we are well trained for it.

Although the training wheels may have come off and I am no longer considered a trainee, I make sure I am diligent in growing and learning at every opportunity. I’ve learned so much in my first year as an attending and can’t wait to see what else is in store.

 

“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.”

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Lilly’s MounjaroTM (Tirzepatide): A New Sheriff in Town

The prevalence of diabetes is increasing at an alarming rate, with more than 34 million Americans suffering from diabetes1. Patients with type 2 diabetes make up 90% to 95% of total diabetes cases1. Type 2 diabetic patients either do not produce enough insulin or develop insulin resistance, resulting in elevation of their blood glucose levels2. The U.S. Food and Drug Administration (FDA) recently, as an adjunct to diet and exercise, approved Eli Lilly and Company’s MounjaroTM (tirzepatide) injection (under the skin, once a week) for Type 2 diabetic patients to control hyperglycemia.  Mounjaro will be offered in 6 different doses, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg, in an auto-injected pen with a pre-attached hidden needle. However, Mounjaro has not been designated to use in Type 1 diabetic patients and is not yet tested for patients with pancreatitis or children under 18 years of age3.

Mechanism of Action of MounjaroTM (tirzepatide):

Eli Lilly and Company’s new drug is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor. GIP and GLP-1 are incretin hormones that are released from intestine upon ingestion of food. GLP-1 stimulates the release of insulin from beta cells of pancreas, increases the number and volume of beta cells, and decreases the levels of glucagon, a hormone also released by pancreas that instructs the liver to release stored glucose in the circulation2. Similarly, GIP also fuels insulin release, promotes beta cell production, and prevents destruction of beta cells2. In Type 2 diabetes, patients do not respond properly to incretin hormones. Mounjaro battles this issue by triggering the activation of GIP and GLP-1 receptor2.

Side Effects of MounjaroTM (tirzepatide):

The most common reported side effects, in at least 5% of patients, are nausea, diarrhea, reduced appetite, vomiting, constipation, indigestion, and abdominal pain. Mounjaro may cause severe side effects including hypoglycemia, pancreatitis, allergic reaction, kidney problems, gallbladder problems, and changes in vision. Further, a warning regarding thyroid cancer is issued; therefore, Mounjaro is not advised to use in patients with personal or family history of Medullary Thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome Type 23.

SURPASS clinical trial program of MounjaroTM (tirzepatide):

The SURPASS trials evaluated the efficacy and safety of Mounjaro for Type 2 diabetes as a monotherapy and as an add-on to other standard care medications. Mounjaro was compared as other injectable medicines like semaglutide (GLP-1 mimic), insulin glargine and insulin degludec. Throughout the five global SURPASS studies, Mounjaro exhibited reduction in A1C among participants having Type 2 diabetes from an average of 5 to 13 years3.

  • SURPASS-1 (NCT03954834): A 40-week study tested the efficacy and safety of three different doses of Mounjaro (5 mg, 10 mg, and 15 mg) as monotherapy in comparison to placebo in Type 2 diabetic patients (naïve to injectable therapy and utilizing diet and exercise alone). Researchers reported that tirzepatide reduced A1C by 1.8% (with 5 mg) and 1.7% (with 10 mg and 15 mg) as compared to 0.1% with placebo. Further, participants lost weight on an average of 14 lb. (5 mg), 15 lb. (10 mg), and 17 lb. (15 mg) whereas participants in placebo group only lost 2 lb3,4.
  • SURPASS-2 (NCT03987919): In this 40-week study, participants were divided in 1:1:1:1 ratio to receive 5 mg, 10 mg, or 15 mg tirzepatide or 1 mg of semaglutide. Mounjaro reduced A1C by 2.0% (5 mg), 2.2% (10 mg) and 2.3% (15 mg) and semaglutide reduced A1C by 1.9%. In a key secondary endpoint, participants in Mounjaro group lost weight by a mean of 17 lb. (5 mg), 21 lb. (10 mg) and 25 lb. (15 mg) in comparison to 13 lb. reduced by semaglutide3,5.
  • SURPASS-3 (NCT03882970): A 52-week study compared the efficacy of previous doses of Mounjaro to insulin degludec (insulin analogue) as an add on to metformin with and without SGLT2 inhibitors. The trial reported 1.9% (5 mg), 2.0% (10 mg) and 2.1% (15 mg) reduction in A1C in patients receiving tirzepatide as compared to 1.3% reduction in patients receiving insulin degludec. Interestingly, participants on Mounjaro lost 15 lb. to 25 lb. depending on the dose, but participants taking insulin degludec gained an average of 4 lb3,6.
  • SURPASS-4 (NCT03730662): A 104-week study compared the efficacy of Mounjaro (5 mg, 10 mg, 15 mg) to insulin glargine in Type 2 diabetic patients with increased risk of cardiovascular disease. Researchers observed a 2.1% (5 mg), 2.3% (10 mg) and 2.4% (15 mg) reduction in A1C in patients receiving tirzepatide as compared to 1.4% reduction in patients receiving insulin glargine. Participants on Mounjaro lost weight (14 lb. with 5 mg, 20 lb. with 10 mg, and 23 lb with 15 mg), whereas insulin glargine group gained 4 lb3,7.
  • SURPASS-5 (NCT04039503): In this 40-week study, the efficacy and safety of Mounjaro as an add on drug to insulin glargine was compared to placebo. An average of 2.1% (5 mg), 2.4% (10 mg) and 2.3%* (15 mg) reduction was observed in Mounjaro group as compared to 0.9% in placebo group. Further, Mounjaro, as an add on drug, reduced body weight by 12 lb. to 19 lb. as compared to placebo group, where participants experienced 4 lb. weight gain3,8.

REFERENCE

  1. National Diabetes Statistics Report. Accessed January 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html
  2. FDA approves trizepatide: A potent new drug for type 2 diabetes. Accessed May 20, 2022. https://www.medicalnewstoday.com/articles/fda-approves-tirzepatide-a-potent-new-drug-for-type-2-diabetes
  3. FDA arrpvoves Lilly’s MounjaroTM (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Accessed May 20, 2022. http://lilly.mediaroom.com/2022-05-13-FDA-approves-Lillys-Mounjaro-TM-tirzepatide-injection,-the-first-and-only-GIP-and-GLP-1-receptor-agonist-for-the-treatment-of-adults-with-type-2-diabetes
  4. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 07 10 2021;398(10295):143-155. doi:10.1016/S0140-6736(21)01324-6
  5. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 08 05 2021;385(6):503-515. doi:10.1056/NEJMoa2107519
  6. Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 08 14 2021;398(10300):583-598. doi:10.1016/S0140-6736(21)01443-4
  7. Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 11 13 2021;398(10313):1811-1824. doi:10.1016/S0140-6736(21)02188-7
  8. Dahl D, Onishi Y, Norwood P, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 02 08 2022;327(6):534-545. doi:10.1001/jama.2022.0078

“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.”

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Join the race against the clock: Controlling for age in cardiovascular disease

The race against aging has already started. People who want part of this race see the limitless opportunities humans will have if aging is taken out of the equation. Humans will be able to live longer with their loved ones, go back to University when they are 70 years old to study this long-dreamed profession they always wanted to try or take the time to go through every single item on their bucket list, no matter how long the list is. Others are worried about what awaits them at the finish line of the race and what sacrifices will have to be made along the way. They argue that aging is the core of our existence and the reason why we make the choices we make every day. If humans don’t age, will they still find a reason to live and would this type of life be worth living? Regardless of people’s scattered opinions, the remaining question to be answered in our race against the clock is: Can we age disease-free?

As humans began to live longer dying less of problems such as hunger, wars and infections, they were faced with a new type of problem: chronic diseases. As we age and get exposed to different environmental and lifestyle factors, a set of biological and functional changes in our bodies lead to the development of chronic diseases such as cardiovascular diseases (CVD), diabetes, cancer, dementia, arthritis, and the list goes on. Notorious for being the ‘number 1 killer in the world’, preventing CVD has been one of the top priorities in our fight against aging. Age is the best predictor of CVD death, and despite years of research and large amounts of funding spent on biomarker discovery, there are currently no better predictors of CVD death than the age of a person and these are some of the reasons why.

Large blood vessels tend to become stiffer over time as they accumulate more collagen (due to an increase in TGF-b activity leading to collagen synthesis from smooth muscle cells) and lose their elastin content (because of higher metalloproteases and cathepsin activity). This leads to a chronic increase in systolic blood pressure which is worsened by the rise of catecholamines levels usually seen during aging. Both phenomena contribute to left ventricular dysfunction and hypertrophy due to the increase in myocardial oxygen demand. Calcification is another hallmark of aging that also contributes to vessel stiffness and induces stenosis. As we age, skeletal calcium is released and tends to accumulate in the vascular structures.

Apart from leading to vessel stiffness, aging causes the vascular endothelial cell (EC) barrier to become dysfunctional. ECs play a crucial role in maintaining vessel integrity and homeostasis by balancing vasodilatory and vasoconstricting functions and by aligning the vessels with an anti-thrombotic surface. Disruption of this protective barrier over time is characterized by ECs undergoing oxidative stress, reduced nitric oxide (a potent vasodilator) production, increased expression of adhesion molecules (ICAM and VCAM) and secretion of inflammatory chemokines (CXCL8) and cytokines (IL-1b and IL-6). The initiating event of atherosclerosis development starts with endothelial dysfunction which gives way for monocyte infiltration and subsequent foam cell formation contributing to plaque development.

At the molecular level, changes affecting the genome and epigenome are a fundamental feature of aging. With age, the clonal diversity of hematopoietic stem cells decreases resulting in the predominance of one clone. In recent years, clonal hematopoiesis of indeterminate potential (CHIP), which occurs as a result of mutations in transcriptional regulators (DNMT3A, TET2 and ASXL1), was found as a novel CVD risk factor, thereby linking genetic mutations in hematopoietic stem cells, aging and CVD. The number of endothelial progenitor cells also decreases over time which reduces angiogenesis capacity and capillary density leading to microvascular disease (such as peripheral artery disease).

The shortening of chromosome telomers is another molecular change related to aging. As cells replicate, telomeres get shorter until cellular senescence is triggered. Cellular senescence is a cellular protective mechanism that activates NK cells to remove cells with defective genetic material via apoptosis. It has been shown that patients with reduced leukocyte telomere length have increased risk of atherosclerosis. An atherosclerotic plaque, rich in inflammatory cells and trans-differentiated smooth muscle cells, is a dense hypoxic environment characterized by the presence of reactive oxygen species which also induce DNA damage and senescence.

Current therapies for atherosclerosis target some of the pathways of aging highlighted above. While statins are known to reduce plaque lipid content and inflammation, in parallel, they tend to increase calcification leading to vascular stiffness. On the other hand, anti-hypertensive treatments offer benefits beyond reducing CVD mortality, but also decreasing dementia. Recently, novel therapies targeting aging in CVD have focused on stem cell therapy. However, clinical trials using cell therapy to improve left ventricular dysfunction or to reduce cardiovascular events have shown no or modest benefit. This may be because autologous cell therapy of stem cells that already have an ‘aging’ phenotype is not ideal, and these cells may require ex vivo reprograming to improve treatment efficiency.

 

Since many age-related diseases have similar underlying molecular mechanisms driving them, the future for treating chronic diseases will rely on targeting the mechanisms of aging rather than treating the disease itself. Some of the best ways to slow down aging is by being active, controlling blood glucose levels, opting for diets rich in antioxidants and fibers and introducing low calorie intake periods during the day. However, this usually requires a substantial effort and serious lifestyle changes on our behalf. But, since research on anti-aging therapies and senolytic drugs is booming, it might be possible to slow down aging by taking one or two pills a day without ever needing to change the routines that we are so comfortable with.

References

  1. Paneni F, Diaz Cañestro C, Libby P, Lüscher TF, Camici GG. The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels. J Am Coll Cardiol. 2017 Apr 18;69(15):1952–67.
  2. Quyyumi AA, Vasquez A, Kereiakes DJ, Klapholz M, Schaer GL, Abdel-Latif A, et al. PreSERVE-AMI. Circ Res. 2017 Jan 20;120(2):324–31.
  3. Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. The Lancet. 2007 Jan 13;369(9556):107–14.
  4. Koopman JJE, Kuipers RS. From arterial ageing to cardiovascular disease. The Lancet. 2017 Apr 29;389(10080):1676–8.
  5. Jaiswal S, Libby P. Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease. Nat Rev Cardiol. 2020 Mar;17(3):137–44.
  6. Antonangeli F, Zingoni A, Soriani A, Santoni A. Senescent cells: Living or dying is a matter of NK cells. J Leukoc Biol. 2019 Jun;105(6):1275–83.
  7. What is the Age of My Heart? – Calculate Your Own Heart Age • MyHeart [Internet]. MyHeart. 2015 [cited 2022 May 16]. Available from: https://myheart.net/articles/what-is-the-age-of-my-heart-calculate-your-own-heart-age/

“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.”

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An Interview with Dr. Ilana Kutinsky- Electrophysiologist and Cardiologist of the Apes

As a resident at Beaumont Hospital, I have the good fortune of working alongside some of the finest cardiologists in the country. I am constantly inspired by talent, innovation, and excellence in patient care. Dr. Ilana Kutinsky, associate professor at Oakland University William Beaumont School of Medicine, takes cardiology and commitment to health equity a step further by providing care to apes throughout the country.

Cardiovascular diseases are the leading cause of mortality not only in humans but also in the great ape species, including gorillas, chimpanzees, orangutans, and bonobos. Established in 2010, the Great Ape Heart Project (GAHP) aims to improve the understanding and management of cardiac disease in our cousin species. A cardiac electrophysiologist by training and profession, Dr. Kutinsky is one of the founders of the Great Ape Heart Project. I sat down with Dr. Kutinsky to learn more about her role as ‘cardiologist of the apes’.

DA: How did you get involved with the Great Ape Heart Project?

Dr. Kutinsky: Around 2000, I was a cardiology fellow at the University of Colorado. During my echo rotation, I picked up a call sitting in the darkroom. “We’re calling from the Denver Zoo. We need someone to come and do TEEs on our gorillas and orangutans. Would you be interested?” and I said “What?”. I talked to my attending and we decided to do it. So, we had Phillips loan us a giant TEE machine and bring it to the zoo. They anesthetized the gorilla and we did the TEE. At the time they were just realizing that captive gorillas die from heart diseases and there was no reference to what is normal. The next month, a female orangutan died from extremis from the anesthesia for the TEE. It was disconcerting to see an animal die for a test we did not even know how to interpret. I got in touch with Dr. Hayley Murphy, who had written a paper reporting echo findings from five gorillas in Boston. We shared our frustration and decided to write a grant to try to collect echos over the country and establish a normal. The grant was rejected but I continued to record readings on my own time by taking freehand measurements on VHS tapes. This is how the Gorilla Heart Project got started. Then it got bigger! We wrote a grant to the Institute of Museum and Library Sciences (IMLS) and got a half a million-dollar grant to set up the Great Ape Heart Project. We were able to hire primatologists, pathologists, veterinarians, and sonographers and set up a database. We have been able to establish normal, identify high-risk animals, and treat heart failure in gorillas. We have consulted on cases not only in the United States but all over the world. It’s a wonderful, although busy hobby for me!

DA: How was your first experience as a cardiologist for the apes, the gorilla in Denver you did the TEE for?

Dr. Kutinsky: It was very similar to taking care of a human once the probe was inside the body. But the animals are enormous, between 350 to 580  pounds. Their chests are like barrels and their skulls are ginormous. To get the TEE probe down their mouths, you have to go past their incisors which are almost the size of my hand.

DA: Were you scared?

Dr. Kutinsky: No, you know they are under anesthesia. And someone is standing in the corner with a big gun. So, if they start to wake up, they will be immobilized. I wasn’t scared because I was so in awe that I was able to do something so amazingly cool. I remember calling my mom afterwards and telling her that every night I spent studying or being on call, all the effort made to get into medical school and cardiology was worth it that day.

DA: Were your co-fellows jealous of you?

Dr. Kutinsky: That’s a good question. Um, I think they thought I was crazy! Doing all that extra work on top of a busy fellowship schedule did not make sense to them.

DA: How is it working with a team of so many disciplines?

Dr. Kutinsky: It is amazing to work with a team of veterinarians, human cardiologists, veterinary cardiologists, sonographers, and pathologists. The vets are honestly some of the smartest people I know. They take care of a 500-pound gorilla with heart disease and then they attend to a tiny bird with an eye injury. Their breadth of knowledge is extraordinary. It has been incredibly rewarding experience working with everyone.

DA: What’s been your most interesting experience being a cardiologist for the apes?

Dr. Kutinsky: Going to Cameroon was one of my most interesting experiences. We were invited by the government of Cameroon to a sanctuary of rescued wild gorillas. We were able to see them up close and interact with them from across a mesh. We were there for 2 weeks, seeing them every day and feeling a connection with them. Usually, I don’t get called when they’re doing well. I’m called when they are sick and about to die, so they’re usually anesthetized. To see them awake, eating and going about their usual life was pretty cool.

DA: Do you have a favorite of the great ape species?

Dr. Kutinsky: Gorillas for sure. I like orangutans too but we don’t have any orangutans in the Detroit zoo so I don’t see them much. Chimpanzees are very naughty and a handful to work with.

DA: Have you become attached to any animal?

Dr. Kutinsky: I was very attached to Sunshine, a gorilla in the Detroit Zoo. He was an old, great animal with a bad heart. He died from influenza a few years ago. I was pretty tight with him. I like Mac in Columbus. He is a very handsome boy. There’s Tatu in Omaha, he’s a good boy. I’ll be sad when they die. Gorillas usually don’t live past 40 years and a lot of the ones with heart disease drop dead early. So we’re hoping to change that.

DA: Do you prefer treating humans or gorillas?

Dr. Kutinsky: Depends on the day! I love animals but I cherish the relationships with my patients. I love my job as an electrophysiologist. Everything I’ve learned as a human doctor I use to treat the gorillas. But if I won the lottery, I would probably devote all my time to the gorillas.

DA: Last question, has taken care of gorillas and other apes affected how you treat your patients? 

Dr. Kutinsky: That’s a great question. Hmm, I guess treating animals has made me a more compassionate doctor and person in general. Since the animals can’t complain or whine, you give them symptoms in your mind. You assume they are hurting or sad, and you try to take care of them. I think it has given me an extra bit of sympathy when I take care of my patients. And it makes me happier in general. When you have a passion, it enriches your whole life.

DA: I guess it was a lucky call that day in the echo lab.

Dr. Kutinsky: Absolutely! I was in the right place at the right time. I also think you have to be open to the universe and do things that are outside the box. I was willing to do the extra work outside of a busy fellowship. I was offered something special and I took it.

 

“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.”

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Women In Cardiology: A Mother’s Day Tribute to Women, Wives, Weekend Warriors, & Workaholics In Cardiology

*Buzz*. Most of us can relate to that alarm going off way earlier than we would like. Wake up, make coffee, throw the clothes in the washer or dryer, clean up the kitchen, put on your office attire or scrubs, and run out the door to start the day taking care of patients, reading nuclear studies, reviewing echocardiograms, or doing catheterizations. For many, this sort of routine is comforting. Enter motherhood or pregnancy to start. This topic in cardiology, a field dominated by men who make up 85% of the workforce, can be an exciting topic to navigate.

The Pregnant Cardiologist

Pregnancy is supposed to be one of the most joyous celebrations in life. I often reminded myself of this while recently pregnant with my second child as I squeezed in OB appointments between patients while simultaneously reassuring them that I would be back after eight weeks. Women in cardiology face obstacles that their male counterparts do not have to use mental bandwidth on. We finish training in our early 30s keenly aware that our “biological clock” is ticking. We try to decide when the right time is to have children whilst trying to grow our own practice and make our footprint. Many questions zoom through our brains. When is the “right” time to take off anywhere from six to twelve weeks with our employer and partners accepting it, covering call, and caring for our patients? How will pregnancy and motherhood affect my career? Is there a maternity leave policy? What if I have complications during pregnancy? Will my partners assume I am going to scale back after I have a child and give preferential treatment to the men? How will pregnancy impact my salary? We sacrifice some of our professional growth to achieve one of the most joyous life events. Or do we? Dr. Martha Gulati, et al recently surveyed women who were members of the American College of Cardiology Women in Cardiology section to assess real life experiences during pregnancy. 341 responded they had children as a practicing cardiologist. Of these, most notified their chair, chief, or practice that they were pregnant in the late first or early second trimester. The most common reason for waiting to report was due to concern of adverse treatment or perception (37.5%). Maternity leave varied dramatically among respondents. The most common leave time was three months (48.9%) followed by less than six weeks (22.6%). 41.2% of respondents had a salary decrease during pregnancy. 37.2% reported performing extra calls or service while pregnant “making up” for being on maternity leave. 21.5% of women thought that taking extra calls or service contributed to pregnancy complications. I must share that I am fortunate to work with some of the most wonderful, understanding, partners and bosses. This was reflected in my pregnancy and leave experience. Not all of us will have a positive experience, but we should. The lack of consistency in maternity leave and support for childbearing is not only a problem in cardiology. We hear this among colleagues of all specialties. Cardiology just so happens to pose a unique challenge given the historical lack of women in the specialty and the rigorous schedule for many. Efforts to create a more uniform maternity leave policy and welcoming pre and post-natal experience are more than past due.

Wonderwomen in Cardiology

Getting back to work after having a child can be overwhelming. The “routine” has changed to a less “routine” routine. That alarm clock buzz is most likely replaced by a crying baby and cold coffee left on the counter somewhere around the house. You are tired. When the sun comes up it is time to feed the baby, get them ready for whatever care you have arranged, and, if breastfeeding, pumping JUST before you leave so you can maximize work time when you arrive. Pumping while doing charts or on zoom calls has become a norm. The concerns about perception at work continue. You wonder, “will I be perceived as fragile or more interested in home life now?”. Struggling to “prove” that motherhood has not taken away your passion for work is almost inevitable. An inherent bias exists. While we juggle motherhood, being a wife (which for many includes cooking, laundry, nighttime routine), and work, we try to convince our colleagues that we are still the same. But are we? I would argue we return better. Finding a group to work with who thinks the same might be hard, but it is attainable. I can attest to that.  Raising children as a cardiologist is a busy new journey. Working together with your spouse is a must. Finally admitting that maybe you cannot do it all at home is okay. Asking for help is okay.  “Subcontracting” household tasks is sometimes necessary to get back to being you: a woman—no, a Wonder Woman both in cardiology and at home. Happy Mother’s Day to all the moms, soon-to-be moms, and those hoping to be moms one day.

Footnote: This was 50% written while pumping and 50% while the children were napping.

REFERENCE

  1. Gulati M, Korn R, Wood M, et al. Childbearing Among Women Cardiologists. J Am Coll Cardiol. 2022 Mar, 79 (11) 1076–1087. https://doi.org/10.1016/j.jacc.2021.12.034

“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.”

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The Protective Role of Anti-Hypertension Medication Among Patients with Comorbidities for COVID-19 Outcomes

Millions of people around the world take Angiotensin-converting enzyme inhibitors (ACEi) and Angiotensin II receptor blockers (ARB) to manage hypertension, heart failure, and coronary artery disease. Concerns of ACEi and ARB potentially increasing the risk of COVID-19 illness severity and mortality among vulnerable populations heightened once scientists reported that risk factors for developing complications included being older, male, and having cardiovascular comorbidities1. One comprehensive study using over 17,000 primary care records found that chronic heart disease has a hazard ratio of 1.57 for COVID-19 related death and the hazard ratio remained high at 1.17 even when accounting for confounding variables, suggesting that people with heart disease are at increased risk of mortality2. In the same study, high blood pressure or hypertension diagnoses were associated with hazard ratio of 0.89, a lower risk of COVID-19 mortality compared to people with normal blood pressure, but insight into how age, sex, comorbidities, and medications influence outcomes were not directly addressed. Such findings fueled a debate about whether ACEI/ARB should be maintained or withdrawn in patients with COVID-19.

The role of ACEi and ARBS drugs in COVID-19 outcomes among cardiovascular patients also became a point of interest due to their mechanism of action in the human body. ACEi and ARB act on the renin-angiotensin-aldosterone system (RAAS), a hormone system important for regulating blood pressure, fluid balance, and inflammation processes that affect cardiovascular health outcomes. While ACEi and ARB drugs are used as the first line of treatment to manage vasoconstriction, there is a question as to how these medications can alter the RAAS balance. In a previous blog, we discussed how the SARS-CoV-2 virus uses the  of angiotensin-converting enzyme 2 (ACE2) receptor to enter host target cells3. This receptor not only acts as the entry point for the virus, but normally acts as a crucial element for regulating RAAS biochemical processes. The inflammatory, tissue damaging, and vasoconstriction effects of Angiotensin II (Ang II) in the body are mitigated by ACE2 activity, and ARB and ACEi drugs also target the Ang II protein4. COVID-19 related research has provided a new understanding of how underlying disease states, behavioral habits like smoking, or genetics could influence ACE2 activity in the body. The unique collaboration between clinicians and scientists during the COVID-19 pandemic has provided new mechanistic insight about how the complex RAAS pathway and the factors that influence disease progression.

Ongoing population studies such as The International Study of Inflammation in COVID-19 (ISIC) and The Michigan Medicine COVID-19 Cohort (M2C2) make use of detailed medical records bio-banked human samples, and advanced statistical modeling to evaluate the potential benefits and harms of ACEi and ARB medications. Using stored blood samples and electronic medical records from patients hospitalized specifically for COVID-19, researchers were able to assess for an association between ACEi or ARB use and in-hospital patient outcomes, such as requiring mechanical ventilation or admission into intensive care. The research team overseeing the ISIC and M2C2 studies analyzed the health outcomes of about 1,600 people hospitalized for COVID-19 and reported that patients taking ACEi or ARB had about 10% mortality compared to 14% who were not on those medications5. Among those taking medications, 24% of patients required ventilation during hospitalization, compared to 20% of those not any treatment. These results were surprising as people taking medication also had significantly more comorbidities such as diabetes compared with the non-ACEi/ARB group. Knowing that people who use ACE inhibitors or ARB are not more susceptible to severe COVID-19 illness or increased risk of mortality during hospitalization has now led to the widely accepted practice of not discontinuing these drugs in people who are infected with SARS-CoV-2. In fact, people on anti-hypertensive medication had lower levels of inflammation biomarkers during hospital admission compared to those who don’t take ACEi and ARB drugs. This insight suggests that ACEi/ARB drugs could counter the inflammatory effects of COVID-19, which could be an interesting future direction of this research. Large scale studies have been valuable for providing evidence on how to mitigate detrimental outcomes during the COVID-19 pandemic and future findings will continue to influence guidelines for monitoring cardiovascular homeostasis, targeting treatments for vulnerable populations, and managing chronic illnesses.

References:

  1. Patel AB, & Verma A. (2020). COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. https://doi.org/10.1001/jama.2020.4812
  2. Williamson EJ, Walker AJ, Bhaskaran K, et al. (2020). Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-436. doi:1038/s41586-020-2521-4
  3. Raizada MK, & Ferreira AJ, (2007). ACE2: A New Target for Cardiovascular Disease Therapeutics. Journal of Cardiovascular Pharmacology, 50(2), 112–119. https://doi.org/10.1097/FJC.0b013e3180986219
  4. Monterrosa Mena, J. ACE-2 and Immune System Changes in Smokers May Underlie COVID-19 Vulnerability. https://earlycareervoice.professional.heart.org/ace-2-and-immune-system-changes-in-smokers-may-underlie-covid-19-vulnerability/
  5. Pan N, Hayek S, the ISIC Group, et al. (2021). Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID‐ Journal of the American Heart Association, 10(24), e023535. https://doi.org/10.1161/JAHA.121.023535

“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.”

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COVID-19 and Endothelial Cell Dysfunction

Photo by CDC on Unsplash

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global health crisis. Cough, fever, and shortness of breath are the most common reported symptoms; however, neurological and gastroenterological manifestations can also be present1. Angiotensin-converting enzyme 2 (ACE-2) has been shown to act as a co-receptor to facilitate coronavirus entry by efficiently binding to the S1 domain of spike protein, a surface glycoprotein of SARS-CoV2. The pathogenesis of COVID-19 depends on the localization of the coronavirus co-receptors. The epithelium of lungs and intestine is rich in ACE-2 expression, thereby providing a possible route of entry for SARS-CoV-2. Further, ACE-2 is also expressed on Type I and type II pneumocytes providing other entry sites for SARS-CoV-2. Virus entry can cause pathological changes at the alveoli-capillary interface. Additionally, copious expression of ACE-2 on the type II alveolar cells can promote rapid viral expansion resulting in further alveolar damage and hyperinflammation3,4.

ACE-2 is also present on endothelial cells, smooth muscle cells, and perivascular pericytes in all the organs, indicating that if SAR-COV-2 is transmitted to the blood circulation, the virus can quickly spread throughout the body3. The postmortem lung tissues of COVID-19 patients exhibited a higher number of ACE-2 positive endothelial cells and a higher prevalence of endothelial injury (disruption of cell membrane and presence of the intracellular virus) and microthrombi than lung tissues of patients who died from influenza-associated respiratory failure1,5. The most common comorbidities observed in COVID-19 patients are hypertension, diabetes, and obesity, all of which are associated with endothelial dysfunction. Further, COVID-19 patients are projected to be at a higher risk of deep vein thrombosis, systemic vasculitis, and acute pulmonary embolism6,7, possibly due to underlying endothelial cell injury and inflammation. Thrombi can directly affect gas exchange and cause and cause multisystem organ dysfunction in COVID-19 pneumonia8. Upon activation, platelets release polyphosphates, which accelerate the activation of factors V and XI, inhibit tissue factor pathway inhibitor and contribute to thicker fibrin strands synthesis. Further, the cytokine release can activate endothelial cells resulting in a prothrombotic environment1.

Acute respiratory distress syndrome is suggested to be caused by the dissociation between lung mechanics, loss of lung perfusion regulation and hypoxic vasoconstriction, and severe hypoxemia9. The loss of hypoxic vasoconstriction can be due to increased mitochondrial oxidative stress resulting in pulmonary endothelial cell dysfunction10. SARS-CoV-2 elements, accumulation of inflammatory cells, intracellular virus, and disrupted cell membranes are detected in the endothelial cells of COVID-19 patients5,11, further indicating endotheliitis /endothelial cell dysfunction during COVID-19 infection. Endothelial cell dysfunction can cause abnormalities in microcirculation in different vascular beds and contribute to life-threatening complications of COVID-19, including thromboembolism and multiple organ damage.

References:

  1. Huertas A, Montani D, Savale L, et al. Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Eur Respir J. 07 2020;56(1)doi:10.1183/13993003.01634-2020
  2. Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 05 28 2020;181(5):1016-1035.e19. doi:10.1016/j.cell.2020.04.035
  3. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. Jun 2004;203(2):631-7. doi:10.1002/path.1570
  4. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 03 28 2020;395(10229):1033-1034. doi:10.1016/S0140-6736(20)30628-0
  5. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 07 09 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
  6. Bompard F, Monnier H, Saab I, et al. Pulmonary embolism in patients with COVID-19 pneumonia. Eur Respir J. Jul 2020;56(1)doi:10.1183/13993003.01365-2020
  7. Criel M, Falter M, Jaeken J, et al. Venous thromboembolism in SARS-CoV-2 patients: only a problem in ventilated ICU patients, or is there more to it? Eur Respir J. Jul 2020;56(1)doi:10.1183/13993003.01201-2020
  8. Poor HD, Ventetuolo CE, Tolbert T, et al. COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis. Clin Transl Med. Jun 2020;10(2):e44. doi:10.1002/ctm2.44
  9. Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 05 15 2020;201(10):1299-1300. doi:10.1164/rccm.202003-0817LE
  10. Guignabert C, Phan C, Seferian A, et al. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. J Clin Invest. 09 01 2016;126(9):3207-18. doi:10.1172/JCI86249
  11. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 05 02 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5

“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.”