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Goodbye Self-Inflicted Intimidation and Hello Learning: A fellow’s experience working with Dr. Rick Nishimura

“Don’t speak out, you may answer incorrectly and embarrass yourself.” This thought was not uncommon during my first two years of fellowship. Yes, I evolved out of this which is why I am sharing my experience. At the same time, I am here to tell you to not make this mistake early in fellowship.

You may or may not have heard of Dr. Rick Nishimura, a master clinician, and educator of cardiovascular hemodynamics. You may have seen his name authored in many of the national guidelines or his face at national and international conferences. Now, imagine him (or your own respective master clinician-educator at your own program) leading weekly hemodynamic sessions and asking escalating difficult questions to the audience. Would you answer? How confident would you need to be to articulate this out loud?

I am about a month away from completing my general cardiology fellowship (my 3 years were slightly extended from two maternity leaves) and I have had time to reflect on my clinical experience. I remember my first year sitting in our auditorium and can vividly recall answering a question about x and y descents incorrectly in front of everyone. I rarely spoke out again for the rest of that year.

As a third-year at the Mayo Clinic, I had the opportunity to work in “Nish” clinic amongst a handful of other fellows and participate in his hemodynamic sessions. Every fellow before me, alongside me, and after me all feel the same way: to work with him requires a great deal of preparation and meticulous chart review of patients, repetitive review of all the guidelines, and an attempt at reading published research relevant to each case. The more I thought about it, it became clear that I had a unique opportunity to challenge myself before graduating. I’m glad I did.

I’d like to share reflections, learning pearls, and takeaways from my experience working with and learning from Dr. Nishimura:

  1. Find passionate clinician educators early in training and don’t be timid about learning from them.

The way he lectures to hundreds of people in a room is the exact way he teaches you and it is incredibly motivating. By explaining complicated pathophysiology with such simplicity, I became deeply entrenched in the learning process. I cannot overemphasize the hours I spent preparing for the potential questions he might ask yet I still left clinic with at least 4+ things to look up, feeling inspired and motivated to be a better learner and educator. This is the art of teaching.

  1. Do a good physical exam and use it to determine whether the rest of the workup is concordant or discordant.

One example I learned was the location of the P2 component of S2 on the chest can tell you the degree of elevated pulmonary pressure.

  1. Look at the data (i.e. echocardiograms) yourself.

Avoid only reading reports as they can sometimes mislead you into making life-altering management decisions for patients. For example, do not accept pulmonary artery systolic pressures without looking at the tricuspid valve regurgitant Doppler profile yourself. Confirm if this was measured correctly because it can change management.

  1. Know the guidelines but understand that not all patients fit perfectly in them.

An elderly woman with severe aortic stenosis may be eligible for both SAVR and TAVI, which stresses the importance of individualization and shared decision-making with the patient and heart valve team.

  1. Communication with the referring provider and follow up with the patient cannot be overstated.

Reaching out to referring providers via letter and phone will develop your communication skills, professionalism, and collaborations. Following up with the patient is not only the right thing to do but also allows you to learn whether your management decision resulted in the best outcome for your patient or if there is a learning opportunity for the next patient who presents similarly.

  1. Teach one another.

Create an environment where you are sharing cases with your co-fellows and colleagues and practice teaching to one another with the hope that one day with dedication you will also inspire trainees.

  1. Lastly, do not be afraid to ask questions and answer questions. Even when you are intimidated.

I eventually told Dr. Nishimura how intimidated I initially felt. If you haven’t had the privilege of meeting him, he is one of the most down-to-earth and welcoming teachers you will ever come across. He laughed and said there was nothing to be intimidated about. Many of the questions you have in your head are also questions others have. In that light, more learning, engaging, and teaching can occur if you allow yourself to.

 

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

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AHA Early Career Voice Vlog: an interview with Dr. Rakesh Gopinathannair

I am excited to interview Dr. Rakesh Gopinathannair, MD for this AHA Blog. We will be discussing “Management of Atrial Fibrillation in Patients with Heart Failure and Reduced Ejection Fraction”. Dr. Gopinathannair was the lead author on the recent AHA Scientific Statement on this topic and will share his valuable insights about this document.

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National and worldwide blood shortage, we need blood! But we don’t want YOUR blood!

Back in Colombia, the minimum age to donate blood was 18 years old, coinciding with the minimum legal drinking age and attending bars. The excitement to party causes a lot of expectancy to everyone’s 18th-year-old birthday, and although I love to party, I was looking forward mostly to be able to donate blood. As I was finishing the first semester of medical school, I had wanted to be a regular blood donor. I saw it as a way of walking the talk of being a physician that wanted to advocate for healthcare beyond the mere consult room, and to be honest, how much does it cost to most of us to donate blood? A few minutes of our time. How much does it mean to someone that needs it? Everything.

On my 18th birthday, before my party, the first order of business was to donate blood as I was finally eligible! I arrived with my mom at the Red Cross, and I filled out some questionnaires and headed to see the physician for further questions. As she reviewed my questionnaire, she mentioned that I had stated that I had sex with men; thus, I was not eligible to donate blood. I was in shock; I tried to explain that I have never had any risky behavior and that, at that recently, I only had sex with a woman. She then elaborated that even if it was with one man, I could not donate blood ever, as I was at risk of transmitting HIV or hepatitis. I then told my mom that my hemoglobin levels were low, so I needed to return in a few weeks. I must admit, this was a heartbreaking moment in my life, which added another layer of burden to the journey of self-acceptance as a bisexual man because my blood was undesirable because of who I am.

The emergency of the HIV and AIDS pandemic during the ‘80s initially identified groups that had a higher risk for having HIV and potentially transmitting it with blood transfusions; these were men who have sex with men (MSM), heterosexual commercial sex workers, and intravenous drug users.1To reduce the risk of transmissions, the FDA put a first donor deferral policy to identify if the persons were in the high-risk groups to prevent them from donating blood. Since 1985 and until December of 2015, the FDA recommended blood establishments to ban FOREVER, indefinitely, for a lifetime, male donors who had sex with another male, even if it was only a one-time encounter. The reason behind this preposterous and anachronic decision, according to the FDA, was “due to strong clustering of AIDS illness and subsequent discovery of high rates of HIV in that population (MSM).”2

In 1988 the Blood Donation Rules Opinion Study (BloodDROPS) found that the prevalence of HIV infection in men that reported male-to-male sexual contact was 0.25%, much lower than the previously thought 11-12%, which could have been a strong argument towards the discriminatory life ban of blood donation to MSM.1

In addition to prejudice-based decisions, a question arises, even if there is a higher prevalence in MSM, doesn’t HIV exist in heterosexual people? Doesn’t their blood get screened as well? Yes, HIV also exists in heterosexual people (currently account for 23% of all HIV diagnoses)3 and yes, ALL blood gets tested. Although surveys rely on the honesty of people and serve as a first screening, according to the CDC, all blood that is collected undergoes rigorous testing for HIV, Hepatitis B virus, HCV, HTLV, syphilis, West Nile virus, and Zika virus.4 Additionally, modern HIV tests can identify HIV as early as ten days after infection.

In 2015 the FDA lifted the lifetime ban for homosexual, bisexual, and MSM to donate blood, if they abstained from having sexual contact with other men for 12 months. Although an improvement from the previous ban, the policy was still highly discriminatory and baseless from science, as it assumes that all homosexual sexual interactions are high-risk interactions. This new policy meant that a male, homosexual, monogamous couple that takes drugs to prevent HIV (PreP) would not be able to donate blood if they did not abstain from sex for a year. Still, a man in a heterosexual monogamous couple that does not use protection was by default consider eligible for donation. Thus, once again, attaching the label of presumptive HIV carrier to all bisexual and gay men.

The latest change on these policies was last year during the peak of the COVID-19 pandemic. Facing severe blood shortages nationwide, the FDA randomly reduced the deferral period of sexual abstinence from 12 months to 3 months; no new data was presented to suggest such changes. 4 Agreeing with what Jon Oliveira said to the American Journal of Managed Care regarding this abrupt policy change, “The FDA’s decision to ease restrictions on blood donations from men who have sex with men proves what medical experts have been saying for decades: that this ban is not based in science but rather discriminatory politics. The FDA’s policy change is a sign of progress—even if forced by the needs of the current crisis—but we must follow the science and continue fighting for a complete end to this archaic, demeaning ban.” 2

The risk of contracting HIV and other blood-transmitted diseases is not linked to one’s sexual orientation or gender identity. They are linked to the actions we take as individuals. Individualizing high-risk behavior (multiple partners, no condom usage, IV drug use, etc.) instead of stigmatizing a particular sexual orientation would still serve its purpose of screening before blood donation. It would allow thousands of bisexual and gay man that want to donate blood. It would put an end to a discriminatory policy that perpetuates the narrative of an unequivocal link between HIV and MSM.

But there is hope after all. While researching for this blog, I found that there is a multicenter clinical trial taking place in various cities ( San Francisco, Los Angeles, New Orlean&Baton Rouge, Memphis, Atlanta, Orlando, Miami, Washington), named the ADVANCED study (Assessing Donor Variability And New Concepts in Eligibility). This pilot study is focused on the FDA’s deferral policy for MSM. The purpose of the study is to determine if different eligibility criteria for a bisexual and gay man can be used, such as an additional history questionnaire, to assess individual risk for HIV, instead of deferring our blood donation according to our last male-to-male sexual contact. The study will be groundbreaking and be the first big step towards changing blood donation eligibility criteria for bisexual and gay men.

I enrolled for the study and will have my first appointment in 3 weeks, I’ beyond thrilled to be part of this trial, so I encourage all bisexual and gay men who reside in these cities to participate in the study. The results of this study are likely to contribute and provide yet another evidence to make the FDA eliminate this prejudice ban permanently. We must gain our dignity in every field of life, and small steps such as getting equal treatment in blood donations is the right step forward.

ADVANCE study: https://advancestudy.org

References:

  1. https://www.fda.gov/media/92490/download
  2. https://www.ajmc.com/view/fdas-revised-blood-donation-guidance-for-gay-men-still-courts-controversy
  3. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics)
  4. https://www.cdc.gov/bloodsafety/basics.html
  5. https://www.cnn.com/2015/12/21/health/fda-gay-men-blood-donation-changes/index.html

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

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Diet, Fat, and Healthy Heart

What type of milk do you prefer? Most people will give you their answers quickly without much hesitation. Besides taste and flavor, whether to choose whole milk (~3.5% fat), reduced-fat milk (2% fat) or skim milk (0% fat) depends mostly on how much fat do you prefer in your diet. Reduced fat milk and skim milk have become the poster children for heart beneficial diets in the past decades. The long-held belief that fat is bad for your heart originates from a famous epidemiology study conducted by Ancel Keys and colleagues1.

Ancel Keys’ Seven Countries Studies influenced dietary recommendation on fat for decades. Keys believed that fatty foods such as dairy products and red meat are the culprit for coronary heart disease. He studied diet, lifestyle, and incidence of coronary heart diseases in about 13,000 adult men in Finland, Greece, Italy, Japan, the Netherlands, the United States, and Yugoslavia1, and found that countries with diets high in saturated fat including the United States have the highest blood cholesterol levels and heart-attack death rates. Based on Keys’ studies and other similar findings, the United States and the United Kingdom introduced dietary guidelines which recommend reducing consumption of saturated fat to about 10% of total energy intake, to lower cholesterol in the blood and therefore decrease the risks of a heart attack. A low-fat diet has been associated with good health practices ever since. Here is a twist to this story, Keys didn’t include France, where the nation’s high-fat diet doesn’t correlate with the occurrence of heart diseases. It turns out to be the opposite.

Not all fat is created equal. Let’s take milk fat for example. Milk fat contains a variety of fats such as saturated fat, unsaturated fat, and trans-fat. Generally, trans-fat is considered as “bad” fat in processed foods and fried foods, however, naturally found trans-fat in milk is beneficial. Another example is cholesterol. It’s taken for granted to associate dysregulated blood cholesterol levels with dietary cholesterol intake. In fact, it’s not cholesterol itself that causes high blood cholesterol levels, but rather the lipoproteins that move cholesterol in and out of cells. Broadly, there are the “good” cholesterol– high-density lipoprotein (HDL) and the “bad” cholesterol­­­– low-density and very-low-density lipoproteins (LDL and VLDL). Seventy percent of milk fat is saturated fat, and saturated fats in milk raise both HDL (good) and LDL (bad) cholesterol. The net effect of milk fat might be neutral. Processed foods, fried foods and stick margarine have lots of trans-fats from production and are known for raising LDL cholesterol and lowering HDL cholesterol.

The “good” and “bad” cholesterol levels are considered as the golden standard for cardiovascular risk prediction. However, recent research shows that high HDL levels in some cases associated with higher risks in heart disease2. The plot is thickened. It turns out that some people with a genetic mutation in HDL receptor gene fail to transport cholesterol outside of blood, therefore results in higher level of fats in the body despite having high levels of HDL cholesterols in the circulation. In conclusion, blindly relying on fat content in the Nutrition label is simply not enough.

Now, let’s go back to the milk choice question one more time. Not only we need to consider what type of fat in cow milk, but we also need to look at other factors too. Sugar is often ignored when it comes to buying milk. Reduced fat and skim milk contain slightly more carbohydrates than whole fat milk does. If your goal is to lose weight by reducing fat content in your milk, you might get disappointed. The relationship between milk fat and weight management is still not clear. An epidemiology study shows that women who consumed more than 1 serving of whole fat milk per day were 15% less likely to gain weight compared to those who drink low fat milk3. Also recent research show that consuming saturated fat does not directly cause heart disease4. Therefore, how much you eat doesn’t necessarily translate to how much will end up in your body. It depends on how you body metabolizes it, what’s your genetic makeup and what else in your diet potentially positively or negatively contribute to the net outcomes. Last not the least, even not all fat creates equal, trans-fat from fried foods and processed foods are still universally considered bad for your health. Try to avoid those if it’s possible.

 

REFERENCE

  1. Keys A. Seven Countries. Harvard University Press; 2013.
  2. Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, et al. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science. 2016;351(6278):1166 LP – 1171.
  3. Rosell M, Håkansson NN, Wolk A. Association between dairy food consumption and weight change over 9 y in 19 352 perimenopausal women. The American Journal of Clinical Nutrition. 2006;84(6):1481–1488.
  4. Weinberg SL. The diet–heart hypothesis: a critique. Journal of the American College of Cardiology. 2004;43(5):731–733.
  5. “The facts on fats infographic” [Image] (2017). American Heart Association. https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/fats/the-facts-on-fats

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

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Patients with concurrent heart failure and kidney disease are not getting proper GDMT

We have all seen the story play out before: a patient with heart failure with reduced ejection fraction (HFrEF) who is new to a hospital system is hospitalized for acute decompensated heart failure. A look at their complete metabolic panel shows a Cr of 2.0 mg/dL (with a corresponding eGFR of 35 mL/min/1.73m2), and despite diuresis, the Cr does not really budge. What was initially thought to be an acute kidney injury from possible renal vascular congestion or from renal hypoperfusion turns out to be a more longstanding chronic kidney disease (CKD). Because the medical team has only met the patient for the first time during this hospitalization and they “do not know where the kidney function is going to shake out,” the patient is perhaps started on a beta-blocker but no other guideline-directed medical therapy (GDMT). The patient is discharged from the hospital on only one guideline-recommended agent. Patients like this, with concurrent HFrEF and CKD, can easily get trapped in a vicious cycle in which they are recurrently hospitalized with heart failure exacerbations and varying degrees of kidney injury; their kidney function becomes an impediment to starting the crucial GDMT which will lower their mortality, reduce their likelihood of being hospitalized again, and even improve their quality of life.

This anecdotal experience is supported by data from a new study published in the Journal of the American College of Cardiology (JACC), “Kidney Function and Outcomes in Patients Hospitalized with Heart Failure.” This study utilized the Get With the Guidelines-Heart Failure (GWTG-HF) registry and analyzed over 365,000 hospitalizations with heart failure, including about 157,000 patients hospitalized for heart failure with a reduced ejection fraction (HFrEF, EF ≤40%). Hospitalized patients had kidney function all across the spectrum, ranging from those with a normal estimated glomerular filtration rate (eGFR) of ≥90 mL/min/1.73 m2 (10% of patients) to those on dialysis (5% of patients). As patients’ eGFR decreased (as kidney function worsened), in-hospital mortality rates for heart failure patients increased from about 1% for those with a normal eGFR to 4-5% for those with an eGFR <30 mL/min/1.73m2 or on dialysis.

Among patients with HFrEF, those with lower eGFR or on dialysis were less likely to be discharged on GDMT such as beta-blockers, mineralocorticoid receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), or angiotensin receptor II blocker-neprolysin inhibitors (ARNI), than those with normal renal function. This pattern was consistent regardless of race/ethnicity and sex. Patients with worse renal function (measured as lower eGFR at time of discharge) were also less likely to have an appointment made after discharge.

These disparities in quality metrics for heart failure patients, particularly those with CKD, are disheartening because 1) many patients with heart failure also have concurrent chronic kidney disease and 2) hospitalized heart failure patients with worse kidney function already experience worse clinical outcomes, such as higher mortality (as shown in this and other studies). Though the use of evidence-based medical therapies is often suboptimal among all patients with HFrEF, patients with comorbid HFrEF and CKD are an especially vulnerable group who would especially benefit from treatment with medications that are proven to improve outcomes. Additionally, though they seem to less frequently have post-discharge outpatient appointments made, these patients would benefit from more (and not less) post-hospital monitoring.

This large contemporary study of patients from a major heart failure registry highlights a gap that we must address among heart failure patients at various stages of kidney disease. More work must be done to prevent or slow the progression of chronic kidney disease in heart failure patients. Finally, special attention should be given to the utilization of guideline-directed medical therapy in this vulnerable population of patients in order to help improve their outcomes, particularly when they are hospitalized for acute decompensated heart failure.

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

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Diabetic medications with benefit in cardiac patients

In the past 1-2 years, strong evidence from randomized clinical trials has shown that certain diabetic medications have benefits in cardiac patients, including improved survival [1-3]. One of these medication classes is Sodium glucose co-transporter 2 (SGLT2inhibitors. The DAPA-HF trial showed the benefit of Dapagliflozin [1], EMPEROR trial showed the benefit of Empagliflozin [2] and CANVAS trial showed the benefit of Canagliflozin [3]. Long-term pharmacologic therapy in patients with heart failure with reduced ejection fraction and chronic kidney disease has been evaluated and proved to have survival benefits and reduce the disease progression through multiple mechanisms. In this blog, we will discuss some of the SGLT-2 inhibitors data, doses in diabetes and heart failure, and some of their common side effects.

Mechanism of action: SGLT2- inhibitors ( -gliflozin ) reduce blood glucose by increasing urinary glucose excretion and they reduce the risk of progression of diabetic kidney disease.

 

Agent name

 

Dose in heart failure patients

 

Usual dose for Diabetes Melleitus

 

Initial eGFR to initiate drug therapy

 

 

Side effects

 

 

 

Empagliflozin

 

 

 

 

10 mg once daily

With/without DM

 

 

 

 

10-25 mg once daily ,  taken with or without food

 

 

 

≥45 ml/minute/ 1.73 m2

 

 

 

-Vulvo-vaginal candidiasis

 

-urinary tract infections

 

-bone fractures

 

-thirst and Increased urine out put

 

– hypovolemia / reduced systolic pressure

 

-acute kidney injury

 

-increased risk of lower limb amputation

 

– DKA

 

-Necrotizing fasciitis (Fournier gangrene)

 

– long-term safety not established

 

 

 

 

Dapagliflozin

 

 

 

 

10 mg once daily

With/without DM

 

 

 

 

5-10 mg once daily , taken with or without food

 

 

 

≥45 ml/minute/ 1.73 m2

 

 

 

 

 

 

Canagliflozin

 

 

 

 

100 mg once daily

With type 2 DM

 

 

 

100-300 mg once daily , taken with or without food

 

 

 

≥30 ml/minute/ 1.73 m2

 Table 1: Summary of the doses, acceptable GFR and side effects of SGLT-2 inhibitors.

Abbreviations: GFR (Glomerular Filtration Rate), DKA (Diabetic Ketoacidosis)

     Contraindications and precautions — SGLT2 inhibitors should be avoided in the following clinical settings

  • Presence of type 1 DM.
  • Presence of type 2 DM with prior diabetic ketoacidosis (DKA) or a condition predisposing to DKA (including pancreatic insufficiency, drug or alcohol addiction).
  • Volume depletion or symptomatic hypotension.
  • eGFR <30 ml per minute per 1.73 m2(except for empagliflozin, for which the threshold is <20 ml per minute per 1.73 m2), end-stage kidney disease, or rapidly declining renal function.
  • Presence of the following conditions :
  • Frequent bacterial urinary tract infections or genitourinary yeast infections. •Presence of risk factors for foot amputation (including those with neuropathy, foot deformity, vascular disease, and/or history of previous foot ulceration).

In conclusion, SGLT-2 inhibitors have shown to have benefits in heart failure with reduced ejection fraction and chronic kidney disease. Health care practitioners, including primary care doctors, cardiologists, endocrinologists, nephrologists, clinical pharmacists and nurse practitioners among other members of the health care team, should familiarize themselves with these medications and their doses in order to provide the best care to our patients.

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and assistant professor at the University of Jordan, who helped me write this blog.

References:

  • McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19. PMID: 31535829.

 

  • Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28. PMID: 32865377.

 

  • Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12. PMID: 28605608.

 

 

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

 

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Cardiac Critical Care Fellowship: Insights From a Fellow Who Recently Completed Her Training

I am pleased to have the opportunity to share the experiences of Dr. Alejandra Gutierrez-Bernal who was one of my general cardiology chief fellows and she recently completed her cardiac critical care fellowship!

Please describe yourself and your prior training.
I am a Latin American woman who loves cardiology, spending time outside, running, swimming, painting, and reading novels. I am the youngest of three and have a baby niece who brightens my days. I was born in Colombia and was fortunate enough to live in different places growing up including Mexico, here in the US and my native Colombia. I did my medical school training in Colombia and then spent some time doing research with my great mentor, Dr. Mina Chung, and Dr. Van Wagoner at the Cleveland Clinic. We studied the molecular mechanisms leading to atrial fibrillation which increased my interest in cardiology as a field. I then did my internal medicine residency at CCF and moved on for my cardiology fellowship at the University of Minnesota. I am currently finishing my critical care fellowship here too.

When and why did you decide to pursue cardiac critical care training?
As a medical student, I was fascinated by cardiology, specifically electrophysiology. I loved to look at ECG’s and try to figure out the exact origin of different PVC’s or arrhythmias. By the end of the residency, I was sure I was going to do electrophysiology. However, during my first year of fellowship, I spent a lot of time in the intensive care unit and everything it involved including VA ECMO, cardiogenic shock, and acute heart failure, and was given enormous autonomy. I found that at the end of the day, I was very tired but felt extremely accomplished and happy. I have had great mentors during my training and one of the people that has influenced me as a person and as a doctor, the most is Dr. Bartos. He is an interventional cardiologist and an intensivist. One day he told me I should think about this as a career and the thought had not occurred to me. The idea stuck with me and now after completing my training I wouldn’t have it any other way.  I have the opportunity to make a difference, establish connections with families and help them when they are most vulnerable. I couldn’t be happier with the choice I have made.

What unique experiences does a cardiac critical care physician who completed a cardiology fellowship have compared to those who pursue cardiac critical care training after completing an anesthesiology residency?
Critical care training is interesting because you work with various specialties. We all have very different perspectives which has made this past year of training so much more enjoyable.  When I approach a patient, I can’t stop myself from looking through the ECG, echocardiogram and think through their hemodynamics imagining what their numbers would be if I had a swan. I manage shock, assess volume responsiveness and fluid status, and use inotropes a little differently given my general cardiology training. My pulmonary critical care colleagues taught me to look at the chest CT and make a mental picture of their pulmonary status and my anesthesia colleagues play with the medications differently. As a cardiologist, the critical care field is very exciting. Our older cardiac patients often have multiple organ systems involved and patients in the other units have more cardiac disease.  This year has been an amazing journey as I go around the other units and look at them from different perspectives, critical care cardiologists fill a gap that was missing.

Why did you choose to stay at the University of Minnesota for cardiac critical care training?
There are three main reasons I wanted to stay here. First and foremost is mentorship. The field of critical care cardiology is newer and having someone to guide me and to aspire to was very important to me. Here I had the opportunity to train with great people who since the early stages of my training pushed me to think out of the box and practice independently, transforming me into a better person and doctor.  The second was the patient population. The University of Minnesota has a great resuscitation team, and we see a multitude of cardiac arrest patients many of whom are treated with VA ECMO. I wanted to have the first-hand experience treating these patients since I believe this is the future of cardiology. And lastly, the research experience. I had protected research time last year which was important to me as I wanted to stay at an academic center and wanted to start building my portfolio in critical care given that my prior research experience had been focused on electrophysiology. Overall, it has been a great experience and I wouldn’t do it any other way.

What are some of the unique aspects of cardiac critical care and general cardiology training at the University of Minnesota?We are lucky enough to have a lot of exposure to mechanical circulatory support. During our general cardiology training, we have several rotations in our intensive care units with our cardiac structural and interventional team which includes our post-arrest patients and the heart failure service with LVAD and transplant patients. We are given a lot of independence with these very sick patients, and I believe that this is what taught me the most and reinforced my decision to pursue critical care. Our cardiothoracic surgeons are very approachable and wonderful team players which makes work so enjoyable and patient care seamless.

What is the balance of your time during your first faculty position (e.g. how many weeks are you on service, do you get protected academic time, etc.)?
I am very excited about starting my first job. I think the balance is perfect for me to start my career. My appointment is 80% clinical and 20% academic. I will have around 13 weeks of service and will be only in the intensive care unit while on service. On my time off service, I will be in the echocardiography lab and will have some clinic. With this, I hope to have a great balance between the sick patients in the ICU and the more relaxing setting  of imaging and general cardiology.

What were you looking for when you were searching for your first attending position?
It was very important for me to be in an academic institution. I like clinical research and the idea of furthering the field is fascinating to me. I was looking for a place that would push me in terms of clinical experience to continue learning and had challenging patients yet provided support and mentorship. The University of Minnesota seemed like the perfect fit. I truly think that what I will be part of, will change the field of resuscitation and save lives, that is why we all signed up for medicine.

What advice do you have for other early career cardiologists?
I think the most important thing is to find and do what makes you happy. If the days are long and tiring but you feel fulfilled at the end of the day, then that is what you should be working for.

Thanks so much for the great advice, Dr. Gutierrez-Bernal!

 

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

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An Experiment with an A.I. Blogging Partner!

This week I wanted to try some new ideas for a blog. Instead of writing it myself, I wanted to test out a new class of artificial intelligence that’s already available, and rapidly expanding in the domain of online media writing. As a blogger, I think it is important to demonstrate what this space is going through in terms of evolution. Therefore, for this monthly blog post, I will be using one of the relatively new Artificial Intelligence (AI) writing generators.

These are applications built on algorithms requiring you to only input a few keywords, or sentences, and then clicking a button and letting the AI generator initiate its programming. The AI will spend some time (only a handful of minutes) and search all over the internet for data, producing a 100% guaranteed unique written article. This type of technology is right now in its infancy stages, and is useful in a limited capacity. But in the next five to ten years, AI of this sort will be immensely more integrated, not just in blogging, but in all types of professional fields.

As a biomedical scientist, I can imagine using an AI generator as an assistant in writing scientific articles that I aim to publish when I generate new research, finalize studies, and have results to share. A medical doctor could use AI writers to assist in composing case reports, as well as discussing details of specific medical treatments, or any other writing task. It’s not hard to imagine a future where many professionals, within academia, or the healthcare system, will be using AI generators to assist them in enhancing, and speeding up content sharing while reducing the time consumption required for writing reports, articles or any other original content.

This is an exciting new technology to embrace as an early career professional. Knowing that my readers (as always, thanks for reading!) are mostly early-career scientists and professionals, I think it’s prudent for me to expose and bring awareness to this emerging technology. With that, I will now share the stage on this blog with the artificial intelligence writing generator called Writesonic. This specific AI generator was picked by me because of its simplicity and affordability. The application only requires me to provide a few keywords, and then provide it time to search and produce a short article that is guaranteed to be unique. There is no “copy-pasting” from somewhere else. And it’s up to me to accept it, and make any changes necessary.

The keywords I provided to seed Writesonic are Heart disease burden novel treatments & prevention strategies. The primer intro I was prompted to provide was this: Heart disease is the number one cause of mortality worldwide. The burden of this disease is set to increase in the coming decades due to longer lifespans, more prevalent sedentary lifestyles, as well as the changing type of diet and food choices that the global population is adapting to. Research towards new preventative measures, as well as new treatment options is of great importance in order to reduce the burden of heart disease on the overall society.

Let’s see what Writesonic produced:

[New Treatments And Prevention Strategies For Heart Disease: A Comprehensive Update

Heart disease is the number one cause of mortality worldwide. The burden of this disease is set to increase in the coming decades due to longer lifespans, more prevalent sedentary lifestyles, as well as the changing type of diet and food choices that the global population is adapting to. Research towards new preventative measures, as well as new treatment options is of great importance in order to reduce the burden of heart disease on the overall society.

What is heart disease?

Heart disease is a term that is used to describe conditions that affect the heart and its chambers (cardiac chamber). Heart disease can be classified as either coronary artery disease or ventricular heart disease. Coronary artery disease is the narrowing of the coronary arteries and the accumulation of plaque, which can lead to a heart attack. Ventricular heart disease is the weakening or malformation of the chambers that give the heart its ability to pump blood, leading to a similar heart attack or a stroke. Approximately 50% of heart disease is due to coronary artery disease. Of this group of diseases, only 50% will progress to cause a heart attack. The remainder are considered non-major conditions, but the symptoms and outcomes can be much worse.

Prevention Strategies

Heart disease is often prevented in its early stages, where the average life expectancy is around 5 years. The first step in the prevention strategies is to prevent a number of risk factors that can cause heart disease, such as high blood pressure, obesity, diabetes, smoking and an unhealthy diet. Some of the proposed strategies for the prevention of heart disease are: Studies show that the common components of heart healthy diets include: vegetables, whole grains, fruit, nuts, low fat dairy products, tea and coffee. Progression to clinical cardiovascular disease can be delayed and even reversed if found in the earlier stages of the disease. Weight gain to obesity may cause a number of health problems, Weight loss is the most important factor in the prevention of heart disease.

Diagnosis and treatment

Heart disease is a major risk factor for death, in both men and women. It is also considered a major cause of morbidity and mortality. Heart disease encompasses all types of conditions in which the heart is significantly damaged. Conventionally, the most common approaches for the treatment of heart disease are drug therapy and surgical intervention. In general, heart disease is caused due to a build-up of atherosclerosis.

Conclusion

Heart disease is a major cause of death worldwide. New therapies and preventative strategies are being developed to reduce the risk of heart disease, as well as new targeted therapies to treat certain forms of the disease. Heart disease is highly complex and the available knowledge and research on the condition is constantly changing.]

 

Alright, I’m back! Here’s my review: Writesonic is one of the better, but not top of the line, expensive options, so presumably there is a level of competence above what we saw here. The user-friendly and low threshold to entry and use of this AI content generator is very attractive. It allows folks like us, outside of the daily need for such a product, to actually jump in and try this stuff out. The actual end-product, the content, is however way below our “subject matter experts” viewpoints, and for many of us, our “technical precision” will quickly find the overly generalized way the AI writes leaves a lot to be desired.

Without burdening you with another example, I did the same exercise with a different AI writing generator called Rytr, which functions similarly to Writesonic. The final content output was remarkably similar in length and depth of information. This research provided me with enough data to understand where the technology has broadly reached. I see no way for these AI assistants and algorithms to be sufficiently up to date with scientific literature and novel science at this moment. Being able to scan and extract information from original research articles and academic publications is a step (or a mile) out of the general AI writer mandate, for the time being (but surely in a few years this will not be the case).

So, in the end, I’ll say this: AI writers have a great potential to be useful in fields of research and medical writing, but for now, they’re a few years away from that utility. Having said that, for early-career professionals, I say keep an eye on this, you’ll probably be using it by the time you’re at a later stage in the career path you’re on currently!

 

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

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I May Have Finished My Training but the Learning Will Never End

Today, as I write this, it’s my last month in the formal term of being a ‘trainee.’ And not just any old trainee but a critical care fellow who’s had 6 years of training under his belt. I started my internal medicine residency in Worcester, Massachusetts – roughly 3000 miles from where I grew up. The population was diverse, the hospital life seemed incredibly exciting (and nerve-racking)

Day of 1 of the intern year with Dr. Deeqo Mohamud who become of my best friends.

and I was far from my family. But, I quickly had a new family – those that I would spend the next 3 years together with.

There is a general feeling and oftentimes unspoken trauma with training. We have endless shifts spanning weekends/holidays, fear of failing, fear of harming our patients, and at times knowing our best efforts may not help save a life. These feelings are often not discussed in residency but I was fortunate to have trained in a place that helped provide me with the support I needed to become the best doctor I could. In fact, I stayed at the University of Massachusetts for an additional 3 years for cardiology training.

I could feel myself growing as a provider during my cardiology training. The responsibilities grew, the fear of mistreating a patient having a heart attack was always on the forefront of my mind, and the expectation that I would be a master of all things related to the heart was

Dr. Noami Botkin (PD) plus my amazing co-fellows, 2 couldn’t make it for the picture.

overwhelming – and still is to this day. I was fortunate to have mentors who helped me grow clinically, academically, and personally. I saw the type of doctor I wanted to become, the changes in medicine that inspired me, and the continued inequalities that broke my heart. The end of my fellowship was marked with a more somber mood due to the COVID-19 pandemic. The ceremonious feeling of finishing residency wasn’t there for any of the trainees who were graduating but true to form, UMass continued to make us feel like family. With the resolve to not let a global pandemic dampen my spirits, I headed back to California after nearly a decade of not living in my home state.

I started yet another fellowship – more training, more weekends, more holidays, and more rewards. I was growing and gaining new skills that were making me a better physician. I was working in various intensive care units across the Stanford Hospital system and all the while, meeting colleagues who become family. COVID was unrelenting and we were all feeling the fatigue of it. The reduced social interactions, the hostile political environment, and our own uncertainty of when things would be back to “normal.” We banded together to provide the support and encouragement needed to get through our shifts.

Stanford Critical Care Fellows posing for the camera

The cumulation of my training has led me to become a critical care cardiologist – a doctor who works in ICUs to take care of any and all aspects of a patient’s heart. As I reflect on my years as a trainee, I’ve realized that the learning will never stop. Not only the science of medicine but the humanity, humility, and courage to do our best daily.

As Dr. Louis Weinstein stated: “At the initiation of your residency, after having received a medical degree, you were legally a medical doctor. Now that you have finished your formal training, you have the potential to become a true Healer.” Having completed my short-term goals of finishing my training, I am now looking to how I can harness Dr. Weinstein’s teachings, to combine elegance into the art and science of medicine. As I start my new position as an attending at the University of Pittsburgh Medical Center, I may no longer be a trainee but I will be a life-long learner.

 

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

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Summary of COVID-19 Medications

The past year has seen tremendous changes due to the coronavirus 2019 (COVID-19) pandemic across multiple levels. While behavioral changes and social isolation helped with limiting the spread of the disease, certain medications were studied and have been shown to be of benefit in COVID-19 patients. In this article, we summarize some of these medications, the mechanism of action and add references to the major studies supporting them.

1-Glucocorticoids — Steroids are recommended for severely ill patients with COVID-19 who are on supplemental oxygen or ventilatory support [1,2].

2-Baricitinib is a selective JAK1 and JAK2 inhibitor used for the treatment of rheumatoid arthritis, and has been used in COVID-19 patients on the basis that it disrupts the activation of downstream signaling molecules and proinflammatory mediators[ 3].

3- Tocilizumab  — Markedly elevated inflammatory markers (including interleukin [IL]-6) are associated with critical and severe COVID-19, and blocking these it may prevent disease progression. Tocilizumab is a recombinant humanized monoclonal antibody that competitively inhibits the binding of interleukin-6 (IL-6) to its receptor (IL-6R) [4].

4Favipiravir is an RNA polymerase inhibitor available in some Asian countries for the treatment of influenza and mild COVID-19, and it is being evaluated in clinical trials for the treatment of COVID-19 in the United States and elsewhere [5].

5-Remdesivir — is an adenosine triphosphate analogue, which stops replication of the virus. It was first described in the literature in 2016 as a potential treatment for Ebola. The FDA granted full approval as a COVID-19 treatment on October 22, 2020, for hospitalized children ≥12 years and adults with COVID-19, regardless of disease severity [6]. 

6Hydroxychloroquine/chloroquine is not recommended in hospitalized patients given the lack of clear benefit and potential for toxicity. There is also for QTc prolongation and arrhythmias with the use of this medication [7].

7Monoclonal antibody therapy –In the United States, the following monoclonal antibody therapies are available for patients with mild to moderate infection in the outpatient setting [8,9]:

Bamlanivimab-etesevimab
Casirivimab-imdevimab
Sotrovimab

8Interferons – Interferon beta has been reported in the literature to inhibit COVID-19 replication in vitro. Defects in type 1 interferon production (which include interferon beta), have been associated with severe COVID-19 infections. However, clinical data so far do not support a clear benefit of interferon beta for severe COVID-19 [10].

9- IL-1 inhibitors – Interleukin-1 (IL-1) is a pro-inflammatory cytokine that has been associated with severe COVID-19, and several observational studies have suggested that IL-1 inhibitors, for example, Anakinra, is associated with reduced COVID-19-associated mortality [11].

10- Colchicine – Although there are some data demonstrating a benefit from Colchicine in mild to moderate COVID-19, the benefit is modest without a reduction in mortality, and adverse effects are common [12].

This is a brief summary of some of these medications. A registry of international clinical trials can be found at covid-trials.org.

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and an assistant professor at the University of Jordan in Amman, Jordan.

References

[1] WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JPT, Horby P, Jüni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Møller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341. doi: 10.1001/jama.2020.17023. PMID: 32876694; PMCID: PMC7489434.

[2] Rochwerg B, Siemieniuk RA, Agoritsas T, Lamontagne F, Askie L, Lytvyn L, Agarwal A, Leo YS, Macdonald H, Zeng L, Amin W, Burhan E, Bausch FJ, Calfee CS, Cecconi M, Chanda D, Du B, Geduld H, Gee P, Harley N, Hashimi M, Hunt B, Kabra SK, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Sabzwari S, Sarin R, Shankar-Hari M, Sharland M, Shen Y, Ranganathan SS, Souza JP, Stegemann M, De Sutter A, Ugarte S, Venkatapuram S, Dat VQ, Vuyiseka D, Wijewickrama A, Maguire B, Zeraatkar D, Bartoszko JJ, Ge L, Brignardello-Petersen R, Owen A, Guyatt G, Diaz J, Jacobs M, Vandvik PO. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379. Update in: BMJ. 2020 Nov 19;371:m4475. Update in: BMJ. 2021 Mar 31;372:n860. PMID: 32887691.

[3] Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, Marconi VC, Ruiz-Palacios GM, Hsieh L, Kline S, Tapson V, Iovine NM, Jain MK, Sweeney DA, El Sahly HM, Branche AR, Regalado Pineda J, Lye DC, Sandkovsky U, Luetkemeyer AF, Cohen SH, Finberg RW, Jackson PEH, Taiwo B, Paules CI, Arguinchona H, Erdmann N, Ahuja N, Frank M, Oh MD, Kim ES, Tan SY, Mularski RA, Nielsen H, Ponce PO, Taylor BS, Larson L, Rouphael NG, Saklawi Y, Cantos VD, Ko ER, Engemann JJ, Amin AN, Watanabe M, Billings J, Elie MC, Davey RT, Burgess TH, Ferreira J, Green M, Makowski M, Cardoso A, de Bono S, Bonnett T, Proschan M, Deye GA, Dempsey W, Nayak SU, Dodd LE, Beigel JH; ACTT-2 Study Group Members. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021 Mar 4;384(9):795-807. doi: 10.1056/NEJMoa2031994. Epub 2020 Dec 11. PMID: 33306283; PMCID: PMC7745180.

[4] Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Graña C, Schmucker C, Bollig C, Henschke N, Sguassero Y, Nejstgaard CH, Menon S, Nguyen TV, Ferrand G, Kapp P, Riveros C, Ávila C, Devane D, Meerpohl JJ, Rada G, Hróbjartsson A, Grasselli G, Tovey D, Ravaud P, Boutron I. Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 Mar 18;3:CD013881. doi: 10.1002/14651858.CD013881. PMID: 33734435.

[5] Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, Kadam J, Wu W, Caracta CF, Tandon M. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021 Feb;103:62-71. doi: 10.1016/j.ijid.2020.11.142. Epub 2020 Nov 16. PMID: 33212256; PMCID: PMC7668212.

[6] Antinori S, Cossu MV, Ridolfo AL, Rech R, Bonazzetti C, Pagani G, Gubertini G, Coen M, Magni C, Castelli A, Borghi B, Colombo R, Giorgi R, Angeli E, Mileto D, Milazzo L, Vimercati S, Pellicciotta M, Corbellino M, Torre A, Rusconi S, Oreni L, Gismondo MR, Giacomelli A, Meroni L, Rizzardini G, Galli M. Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacol Res. 2020 Aug;158:104899. doi: 10.1016/j.phrs.2020.104899. Epub 2020 May 11. PMID: 32407959; PMCID: PMC7212963.

[7] Rochwerg B, Siemieniuk RA, Agoritsas T, Lamontagne F, Askie L, Lytvyn L, Agarwal A, Leo YS, Macdonald H, Zeng L, Amin W, Burhan E, Bausch FJ, Calfee CS, Cecconi M, Chanda D, Du B, Geduld H, Gee P, Harley N, Hashimi M, Hunt B, Kabra SK, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Sabzwari S, Sarin R, Shankar-Hari M, Sharland M, Shen Y, Ranganathan SS, Souza JP, Stegemann M, De Sutter A, Ugarte S, Venkatapuram S, Dat VQ, Vuyiseka D, Wijewickrama A, Maguire B, Zeraatkar D, Bartoszko JJ, Ge L, Brignardello-Petersen R, Owen A, Guyatt G, Diaz J, Jacobs M, Vandvik PO. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379. Update in: BMJ. 2020 Nov 19;371:m4475. Update in: BMJ. 2021 Mar 31;372:n860. PMID: 32887691.

[8] Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM; BLAZE-1 Investigators. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):229-237. doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28. PMID: 33113295; PMCID: PMC7646625.

[9] Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17. PMID: 33332778; PMCID: PMC7781102.

[10] WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernández García C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, García PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portolés A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Røttingen JA, Swaminathan S. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med. 2021 Feb 11;384(6):497-511. doi: 10.1056/NEJMoa2023184. Epub 2020 Dec 2. PMID: 33264556; PMCID: PMC7727327.

[11] Huet T, Beaussier H, Voisin O, Jouveshomme S, Dauriat G, Lazareth I, Sacco E, Naccache JM, Bézie Y, Laplanche S, Le Berre A, Le Pavec J, Salmeron S, Emmerich J, Mourad JJ, Chatellier G, Hayem G. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2020 Jul;2(7):e393-e400. doi: 10.1016/S2665-9913(20)30164-8. Epub 2020 May 29. PMID: 32835245; PMCID: PMC7259909.

[12] Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinèz-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. PMID: 32579195; PMCID: PMC7315286.

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