AHAFIT – Page 3 – The Early Career Voice

The Needle Moves Slowly on MINOCA

January 18, 2022January 11, 2022 Bhavya Varma, MD

I remember being a medical student and listening to a podcast where I first heard the term MINOCA (myocardial infarction with nonobstructive coronary arteries) in 2019. I was deciding between internal medicine and OBGYN at this time, and learning about heart disease specific to and common in women naturally grasped my attention. Dr. Bairey Merz from Cedars-Sinai provides a fantastic overview of the disease process and evaluation. I kept thinking about all the ways we’ve made incredible strides in heart disease over the years. Now, I was thinking they were unequal.

Dr. Brent Gudenkauf, a PGY-2 at the Johns Hopkins Hospital, et al. recently published a review in the Journal of the American Heart Association entitled “Role of Multimodality Imaging in the Assessment of Myocardial Infarction with Nonobstructive Coronary Arteries: Beyond Conventional Coronary Angiography”¹. They do a wonderful job of taking us through diagnostic criteria, preferred imaging modalities, and guideline recommendations regarding MINOCA. This term is still not commonplace outside of cardiology, and in the early days some thought these patients were having “false positive MIs” as they outline in the paper. This led to mostly women missing out on necessary diagnostic work up and targeted therapies. Today we have specific diagnostic criteria from the AHA and ESC including positive serum myocardial biomarkers and clinical evidence of MI (which can include ischemic symptoms, new ST segment changes, new LBBB, new pathologic Q waves among others) and no epicardial coronary lesions >50% stenosis on angiography.^2,3

What I find disheartening is how slowly our needle has moved in terms of therapies. As they highlight in this paper, even after diagnosis of MINOCA 25% of patients continue to experience angina⁵ and experience worse quality of life compared with MI-CAD (MI associated with obstructive coronary artery disease) due to persistent anginal symptoms and inadequate treatment with existing antianginal therapies. They were less often treated with beta blockers and less often referred to cardiac rehab⁵. It is clear that this patient population of majority young women is faring worse than its traditional myocardial infarction counterpart in terms of therapies and quality of life.

For these reasons, we should all develop a good understanding of diagnostic pathways and targeted treatments. The recommended imaging modality is IVUS (intravascular ultrasound) or OCT (optical coherence tomography) ^2,4. As a young trainee myself, I am not familiar with either of these modalities and was introduced to these concepts via #AHA21. OCT is an optical analogue of IVUS and can “differentiate tissue characteristics such as fibrous, calcified, or lipid-rich plaque and identify thin-cap fibroatheroma”⁶. During PCI, OCT can also provide information about dissection, tissue prolapse, and thrombi⁶; this is significant given SCAD (spontaneous coronary artery dissection), in situ thrombosis, and epicardial and microvascular spasms are all causes that can lead to MINOCA¹. Cardiac MR is also useful when MINOCA is suspected as it will show late gadolinium enhancement and can also uncover mimics like myocarditis and Takotsubo cardiomyopathy. Additionally, if embolism to coronary arteries is suspected then thrombophilia workup is recommended. They do a wonderful job outlining this algorithm in Figure 2 in the paper by Gudenkauf et al.¹We should all be working to familiarize ourselves with this figure and its recommendations and integrating this into our evaluation for chest pain.

Although the advancements in diagnosis and evaluation are exciting and important, there are no randomized clinical trials evaluating treatments for patients with MINOCA. The MINCOA-BAT trial is an upcoming randomized multi-center study which will hopefully help to move the needle forward in evidence-based targeted therapies (clinicaltrials.gov, NCT 03686696). This excellent review by Gudenkauf et al should be shared widely as this is an important and still too often underdiagnosed and undertreated condition among our patients.

References

Gudenkauf, B., Hays, A. G., Tamis‐Holland, J., Trost, J., Ambinder, D. I., Wu, K. C., Arbab‐Zadeh, A., Blumenthal, R. S., & Sharma, G. (2021). Role of multimodality imaging in the assessment of myocardial infarction with nonobstructive coronary arteries: Beyond conventional coronary angiography. Journal of the American Heart Association. https://doi.org/10.1161/jaha.121.022787
Tamis‐Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian‐Engoren C, et al. Contemporary diagnosis and management of patients with myocardial infarction in the absence of obstructive coronary artery disease: a scientific statement from the American Heart Association. Circulation. 2019; 139:e891–e908. doi: 10.1161/CIR.0000000000000670
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli‐Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST‐segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST‐segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018; 39:119–177. doi: 10.1093/eurheartj/ehx393
Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, et al. ESC working group position paper on myocardial infarction with non‐obstructive coronary arteries. Eur Heart J. 2017; 38:143–153. doi: 10.1093/eurheartj/ehw149
Grodzinsky A, Arnold SV, Gosch K, Spertus JA, Foody JM, Beltrame J, Maddox TM, Parashar S, Kosiborod M. Angina frequency after acute myocardial infarction in patients without obstructive coronary artery disease. Eur Heart J Qual Care Clin Outcomes. 2015; 1:92–99. doi: 10.1093/ehjqcco/qcv014
Terashima, M., Kaneda, H., & Suzuki, T. (2012). The role of optical coherence tomography in coronary intervention. The Korean journal of internal medicine, 27(1), 1–12. https://doi.org/10.3904/kjim.2012.27.1.1.

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

Solutions to Cardiology D&I Connection

December 9, 2021December 8, 2021 Mary Branch, MD, MS

Now that we know the harmful myths, importance & benefits of inclusion, as well as steps towards inclusion of BIPOC in cardiology. I hope we are aware too that this is not a zero sum game and we all can benefit by practicing together in this field.

So, what is the answer? Well, from someone who has integrated many spaces growing up, I know. You find connection, you learn from one another, and you grow.

The same principles can apply for all. Here are some final thoughts about how we can achieve cardiology workplace equity.

Communication

We all have one thing in common. We’re human. Finding commonality with trainees can help bridge any gaps and change biases. Socializing in the beginning to get to know people can be one way to start. This fosters good relationships and we all start on equal ground and build trust. It can be helpful also to check-in. These conversations can be open and honest in a safe space to share experiences (without judgement and non punitive).

Benefit of the Doubt

This is an important principle. With bias and hierarchy this can manifest into lack of benefit of the doubt. Many trainees who graduate medical school are smart. After a certain IQ, there is a marginal difference (discussed in Outliers by Malcolm Gladwell). If a mistake is made, assume the person is smart and discuss better strategies moving forward. It helps to give each other grace. Being clear about your own biases may address this issue. Negative actions stemming from bias and hierarchy can play out during frustration or stress. This can make an uncomfortable environment for the trainees. Consider addressing issues in your own life and this may be a remedy to this issue. We all have bias and personal issues, building awareness is a starting point.

Sponsorship

Once a trainee makes it through medical school and residency, they are smart and have endurance. Those who have drive and passion can likely be molded into successful researchers, teachers, and bedside clinicians. One way to help build community and help it grow in training is sponsorship. This can include recommendations for research projects or offering to bring them along to a talk or presentations (hopefully will be in-person soon). It can be fun to be a part of someone’s journey.

For BIPOC medical students and trainees

The above principles apply to us too. In any situation, it helps to look at the man/woman in the mirror and take accountability. We can recognize our own bias and ego. We also can work strategically towards excellence. Remember that at the end of the day; game recognize game. Further, we can determine how we may be holding ourselves back with imposter syndrome. You belong on that wall too! Some of us carry generational weight and feel the need to represent an entire community. You don’t have to hold that weight and can let go. Consistently remember to keep your eye on the prize and rise above the mellow drama. Just hold on. This too shall pass. There is a reckoning in this country; and this is the time to step out into the light. You are worthy.

This essay does not include every principle. Recommendations for how to connect can also be program specific. Many may grumble about these efforts and worry there will be a reversal of inequity. It’s important we swing the pendulum back to the center first. This takes intentionality. We all will benefit from this work to make a more peaceful environment. This can translate to improved patient outcomes and address health disparities, if we start from within.

Health Equity, the Forgotten Pillar

November 15, 2021November 15, 2021 Ayana April Sanders, PhD

This year’s AHA21 Scientific Session placed an intense spotlight on understanding and achieving health equity in cardiovascular health (CVH). AHA has a broad vision for being transformative in all of the ways that structural inequities influence health outcomes. Specifically, AHA’s 2024 Impact Goal states that: Every person deserves the opportunity for a full, healthy life. As champions for health equity, by 2024, the American Heart Association will advance cardiovascular health for all, including identifying and removing barriers to health care access and quality.

On Day 1 of AHA21, during the ‘Cardiovascular Health After 10 Years: What Have We Learned and What is the Future?’ session, we engaged with experts about the genesis of CVH, how it has been studied throughout the life span over the past decade, and methods for influencing CVH at critical life stages. Darwin Labarthe, MD, MPH, PhD, provided a historical review of the conceptual origins and definition of CVH, and the meaning of CVH in translation. CVH is defined by key features of AHA’s Life’s Simple 7, including assessments of diet, smoking status, physical activity, weight management, blood pressure, cholesterol, and blood glucose.

Ideal CVH is determined by the absence of clinically diagnosed CVD together with the presence of the 7 metrics. Longitudinal evidence has shown that maintaining ideal CVH is more cardioprotective than improving and achieving CVH from a lower CVH level. But US NHANES data shows that about 13% of adults meet 5 of the 7 criteria, 5% have 6 of 7, and virtually 0% have ideal CVH or meet 7 of 7 metrics. This begs the question of how do we attain and maintain a high level of CVH? Ideally, maintaining CVH by Life Simple 7 standards should be SIMPLE…just ensure that all 7 metrics are met, and you will have ideal CVH! But realistically, it is near impossible for individuals to achieve ideal CVH. It is more likely that both individual and population-level efforts are needed to achieve and maintain CVH.

From a life course perspective, high CVH in adulthood is more likely when high CVH is present in early life. But as the panelist continued to describe the state of CVH in America, we quickly learned that while high CVH is consistently associated with lower risk of cardiovascular disease (CVD), disparities in CVD rates vary by sociodemographic factors like age, sex, race/ethnicity, and educational attainment. A recent study by panelist Amanda Marma Perak, MD, MS, FAHA, FACC, and colleagues (2020) using data from the CARDIA study found that less than a third of young adult participants had high CVH, and this was lower for Blacks than Whites and those with lower than higher educational attainment. These results demonstrate that CVH is far from ideal even among younger cohorts. Over the last few decades, we have witnessed increasing rates of cardiovascular abnormalities and subclinical and overt CVD in adolescents and emerging or young adults. The low prevalence of ideal CVH in young adults suggests that factors contributing to CVD risk may be embedded at earlier life stages. The experiences that happen or do not happen in early life settings (i.e., family, households, schools, communities, etc.) are important opportunities to achieve or maintain high CVH. The drivers of health disparities, like social determinants of health (SDOH), structural racism, and rural health inequalities, are necessary to achieve sustainable health equity and well-being for all. One method is effectively developing culturally-tailored community-engaged partnerships to promote CVH. LaPrincess Brewer, MD, MPH, shared the phenomenal community-based interventions being conducted to intervene on low CVH in Black neighborhoods by addressing SDOH at the community-level. These included the Fostering African-American Improvement in Total Health CVH (FAITH!) CVH wellness program, Community Health Advocacy and Training (CHAT) program, and The Black Impact Program.

The conversation on CVH and health equity continued strong on Day 2 of AHA21 at the ‘Achieving Health Equity: Advancing to Solutions’ session. With a panel of leading experts in health equity research, calls for action rang out at each presentation. David Williams, PhD, argued that racial inequalities in health are fortified from centuries of established institutional/structural racism, individual discrimination, and cultural racism, which result in a significant cost to mental health and millions of African-American lives lost each year. Sonia Angell, MD, MPH built on the discussion with a call to action in investing in understudied and marginalized communities that experience poorer CVH. Importantly, as clinicians, research scholars, and policymakers, we need to consider the significant impact of spending more time addressing intervention areas with the largest impact on health, like the structural causes of health inequities. When we work to eliminate structural causes of health inequities, we can begin to spend less time and energy working on small impact areas like counseling, education, and referrals for emergency foods and housing. Ultimately, we can reduce the time and costs of mitigating health inequities when we focus on eliminating the structural causes of health inequities.

Finally, in a powerful video, Health Equity: Patients’ Perspectives, we were invited to hear the stories and experiences of those from Black and Hispanic/Latino communities who were significantly affected by health inequities and failed by their healthcare systems. The tales were jarring and left the audience and panel with a strong sense of remorse. The impact of inequalities in health has been a regular staple in marginalized communities across America for centuries. Collectively, from these voices, we recognize that patients and participants need to be treated as humans. In seeking to meet AHA’s 2024 Impact Goal, I want to echo the sentiments of Kirsten Bibbins-Domingo, PhD, MD, MAS, that equity was always an important pillar in health quality and safety, but it is the forgotten pillar. We must make health equity front and center. As such, we need to 1) actively make health equity a priority and place it front and center in our professional and personal work; 2) have respect for all of humanity from all social groups; and 3) we need better science to understand how risk and disease are being experienced.

References

Lloyd-Jones, Donald M., et al. “Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond.”Circulation 4 (2010): 586-613.
Enserro, Danielle M., Ramachandran S. Vasan, and Vanessa Xanthakis. “Twenty‐year trends in the American Heart Association cardiovascular health score and impact on subclinical and clinical cardiovascular disease: the Framingham Offspring Study.”Journal of the American Heart Association 11 (2018): e008741.
Benjamin, Emelia J., et al. “Heart disease and stroke statistics—2017 update: a report from the American Heart Association.”circulation 10 (2017): e146-e603.
Perak, Amanda M., et al. “Associations of late adolescent or young adult cardiovascular health with premature cardiovascular disease and mortality.”Journal of the American College of Cardiology 23 (2020): 2695-2707.
He, Jiang, et al. “Trends in Cardiovascular Risk Factors in US Adults by Race and Ethnicity and Socioeconomic Status, 1999-2018.”JAMA 13 (2021): 1286-1298.

#AHA21: Matching Into Cardiology Fellowship: The Inside Scoop from Program Directors

November 14, 2021November 14, 2021 Bhavya Varma, MD

We were lucky enough to hear from some exceptional PDs and APDs during #AHA21. The process of applying to cardiology fellowship can be daunting. These discussions provide amazing tips and insight on the process so we can best prepare.

What catches your eye on CVs?

Although this will vary by program and individual, a few themes were consistent amongst the panelists. Most programs and directors will be looking for continuation of a story and a common thread between your research, personal statement, and letters. You want to convey who you are and why you have an interest in cardiology. “It’s a two-way street” meaning fellowships also function as a part of a larger clinical and research program. They look for applicants who will fit into their culture and further the values of their program.

Additionally, PDs and APDs will look at the residency training programs, whether you are local and want to stay local, and your research. For your research projects, multiple panelists mentioned quality was more important than quality. The emphasis was showing you could follow a project to completion. “More than case reports or review articles, I look for a substantive experience in research.”

How much weight do you put on the personal statement? Should anything be avoided?

This should be used as a place to tell your story. “What attributes does this person have that will put their trajectory where we want our fellows to go? Does this person have resilience, are they able to turn disadvantages into advantages?”

The main themes that came across in the panelists answers to this question were humility, resilience, and a willingness to learn. Additionally, multiple people highlighted that this is a good place to address anything unusual that could cause confusion in your application – do you have an unusual timeline? Are there gaps in your career? Did you take breaks to do other things? They also mentioned that this would be a great place to highlight how your background prior to medicine/hobbies lend to your interest in cardiology. With this in mind, it’s important to remember this is different than a medical school application and you should be cautious with how provocative or creative you are in your writing. It was also mentioned that you can emphasize your love of a subspecialty but should also remain open-minded to the field as a whole. “The point of fellowship is to introduce you to the field so you can navigate the next steps in your career” and multiple panelists mentioned numerous fellows change their focus throughout fellowship and exploring is encouraged.

Tips for the virtual interview?

“It can be challenging to convey your narrative when you’re not in person. Find a way to project your narrative to someone who may have nothing in common with you.” Make sure you practice this with a loved one or your colleagues. Recognize your ticks, be careful when you’re reading from your screen when answering questions because interviewers notice. Applicants should also be aware that they will be asked behavioral questions (Ex. Tell me about a mistake you made when caring for a patient. Tell me about a challenging patient interaction). Practice these beforehand and think ahead about the kinds of answers you might give.

Be aware of how you look on your camera. Record a mock interview on zoom and watch it. Even small details like lighting and not have distracting objects placed in your screen can have a big impact in the age of virtual interviews. Attend the program orientation session the evening before. Do not turn off your camera, dress professionally, and don’t be late to zoom sessions. Research the program and ask the faculty about it! Show them you are invested and know about the program. It is still not clear whether interviews will be virtual or in-person for the next interview cycle.

Post-Interview Communication?

The main advice here was similar to what we heard during residency interviews: do not lie. Do not tell multiple programs they are your number one choice. Keep in mind, many people change their mind throughout the interview season and ultimately you do not want to make decisions early in the process. With this in mind, telling a program you are enthusiastic and interested can be very helpful. This is especially true during virtual interviews, where it can be difficult for programs to gauge interest and investment. If you genuinely feel you found your top choice, most programs encourage hearing from you. If you are trying to match to a different geographical location, this can also be a good opportunity to reiterate the reasons you want to move. Notably, you need to be mindful about over-communication.

Hearing from those on the other end of the interview process was an excellent opportunity to focus on what is important. Ultimately, its about your love for cardiology and passion for furthering the field! Find you network and enjoy this time as you explore and determine what you want to do in your career.

This program is part of the FIT Program at #AHA21. The panelists include Drs. Eric Yang, Salim Virani, Carlos Alfonso, Naomi Botkin, Melvin Echols and was moderated by Drs. Aubrey J Grant and Agens Koczo. All FIT program at AHA Scientific Sessions were produced and moderated by FITs for FITs.

Anti-platelet therapy in STEMI

August 23, 2021August 17, 2021 Lina Ya'qoub, MD

ST-elevation myocardial infarction (STEMI) is considered a medical emergency globally, where the patient must seek medical help immediately. The treatment plan for this condition involves reperfusion therapy with or without stent placement, controlling the comorbidities and using specific medications to reduce the risk of recurrence and future complications.

One of the major drug categories is the antiplatelet therapy. So we will discuss briefly the different types of anti-platelet drugs used in STEMI and the different patient scenarios in STEMI. [1][2]

A-Antiplatelet Therapy to Support Primary PCI

1- Aspirin

– Loading Dose of 162 to 325 mg should be given before primary PCI, to be chewed or crushed to establish a high blood level quickly. (More rapid absorption occurs with non-enteric-coated formulations).

– After PCI, aspirin 81 -325 mg should be continued indefinitely (81 mg is the preferred dose)

2- P2Y12 receptor inhibitors

– A loading dose of a P2Y12 receptor inhibitor should be given as early as possible before or at time of primary PCI. Options include one of the following:

Clopidogrel 600 mg

US FDA has highlighted the potential impact of CYP2C19 genotype on clopidogrel pharmacokinetics and clinical response ( e.g: drug interaction with PPI ) . Nevertheless, other studies have not confirmed associations è Future studies are needed to further clarify the risk .[3]

Prasugrel 60 mg

NOT to be administered to patients with a history of stroke or transient ischemic attack and was not shown to be beneficial in patients ≥75 years of age or patients who weigh <60 kg.[4]

Ticagrelor 180 mg

** Prasugrel and Ticagrelor are preferred to clopidogrel. [5] [6]

– P2Y12 inhibitor therapy should be given for at least 1 month in patients with BMS and at least 6 months in patient with DES, using the following maintenance doses: [2]

(( This duration can be extended or reduced according to the patient specific ischemic and bleeding risks )).

Clopidogrel 75 mg daily
Prasugrel 10 mg daily
Ticagrelor 90 mg twice daily

3- GlycoProtein(GP) IIb/IIIa receptor antagonist

– these drugs are given at the time of primary PCI (with or without stenting or clopidogrel pre-treatment) in selected patients with STEMI who are receiving unfractionated heparin (UFH).

– patients who might benefit from a GP IIb/IIIa inhibitor include those who are found to have no or slow reflow, large thrombus burden, or intraprocedural bailout for distal embolization, coronary artery dissection, or hemodynamic instability.

Options include the following :

a.Abciximab:

-dose of 0.25-mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min)

b.high-bolus-dose Tirofiban :

– dose of 25-mcg/kg IV bolus, then 0.15 mcg/kg/min

– In patients with CrCl <30 mL/min, reduce infusion by 50%

c.Double-bolus Eptifibatide :

– dose of 180-mcg/kg IV bolus, then 2 mcg/kg/min; a second 180-mcg/kg bolus is administered 10 min after the first bolus.

– In patients with CrCl <50 mL/min, reduce infusion by 50%

– Avoid in patients on hemodialysis.

B-Antiplatelet Therapy With Fibrinolysis at a Non–PCI-Capable Hospital

1-Aspirin

– 162- to 325-mg loading dose

– should be continued indefinitely ( 81 mg is the preferred dose)

AND

2-P2Y12 receptor inhibitors

– Clopidogrel

– 300-mg loading dose for patients <= 75 years of age

– 75-mg loading dose for patients >75 years of age

– followed by: 75 mg daily should be continued for at least 14 days and up to 1 year

– prefer clopidogrel in this scenario over ticagrelor or prasugrel due to the increased risk of bleeding with the latter two. (( pretreatment with ticagrelor or prasugrel is considered a relative contraindication to fibrinolytic therapy )) [7]

C-Antiplatlet therapy when Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy

1-Aspirin

– 162- to 325-mg loading dose

– 81- to 325-mg daily maintenance dose (indefinite)

– 81 mg daily is the preferred maintenance dose

2- P2Y12 receptor inhibitors

– Clopidogrel

– if the patient’s Age <= 75 years: 300-mg loading dose

– if the patient’s Age >75 years: no loading dose, give 75 mg

– Followed by 75 mg daily for at least 14 days and up to 1 year in absence of bleeding

D- Urgent CABG

1-Aspirin

– should not be withheld before urgent CABG

2- P2Y12 receptor inhibitors

– Clopidogrel or ticagrelor should be discontinued at least 24 hours before urgent on-pump CABG, if possible.

– Urgent CABG within 5 days of clopidogrel or ticagrelor administration or within 7 days of prasugrel administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.

3- GlycoProtein(GP) IIb/IIIa receptor antagonist

– Short-acting intravenous agents (eptifibatide, tirofiban) should be discontinued at least 2 to 4 hours before urgent CABG.

– Abciximab should be discontinued at least 12 hours before urgent CABG

– Urgent off-pump CABG within 24 hours of clopidogrel or ticagrelor administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.

The following table discusses some differences between P2Y12 receptor inhibitors.

P2Y12 receptor antagonist

Mechanism of binding

Loading dose

Maintenance dose

Prodrug

Comments

Clopidogrel

Irreversible

Inhibitor

300 mg

600 mg

75 mg once daily

Yes

The drug needs to be metabolized into its active form

-Warnings/Precautions:

1-Bleeding risk

2-Thienopyridine hypersensitivity

3-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks

– to be discontinued at least 5 days before surgery

Ticagrelor

Reversible inhibitor

180 mg

90 mg twice daily

-Warnings/Precautions:

1-Bleeding risk

2-Bradyarrhythmias and Ventricular pauses

3-Hyperuricemia

4-dyspnea

5-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks

– to be discontinued at ≥5 days before surgery.

Prasugrel

Irreversible inhibitor

60 mg

10 mg once daily

Yes

The drug needs to be metabolized into its active form

-Warnings/Precautions:

1-Bleeding risk

[US Boxed Warning]: Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke.

2-Hypersensitivity

3-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks

– to be discontinued at least 7 days before surgery

Table (1) : Summary of P2Y12 Receptor antagonist agents dosing, pharmacokinetics and adverse effects.

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.

Reference:

[1]- 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

[2]- 2016 ACC/AHA Guideline: Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease

[3]-Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Writing Committee Members, Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA Clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation. 2010 Aug 3;122(5):537-57. doi: 10.1161/CIR.0b013e3181ee08ed. Epub 2010 Jun 28. PMID: 20585015.

[4]-Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4. PMID: 17982182.

[5]-Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30. PMID: 19717846.

[6]-Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4. PMID: 17982182.

[7]- Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, McCabe CH, Braunwald E; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005 Mar 24;352(12):1179-89. doi: 10.1056/NEJMoa050522. Epub 2005 Mar 9. PMID: 15758000.

Drugs in Gestational Hypertension

August 18, 2021August 17, 2021 Lina Ya'qoub, MD

Gestational Hypertension (GHTN) is defined as the new onset of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg , on at least 2 occasions 4 hours apart , at or after 20 weeks of gestation in a previously normotensive woman . It is considered as one type of the major hypertensive disorders in pregnancy; which also includes Pre-eclampsia, eclampsia and chronic hypertension. [1]

Hypertensive disorders of pregnancy is one of the leading causes of maternal and perinatal mortality. It can complicate the pregnancy leading to multi-organ damage such as renal failure, liver failure, pulmonary edema, fetal growth retardation and cerebral symptoms. [1]

The main target in controlling the maternal BP readings is to reduce the risk of maternal stroke and heart failure. So we will talk briefly about the medications used during pregnancy that are considered safe to achieve this target.

* First-line Oral Drugs used to treat NON-severe HTN in pregnancy , the choice among these agents is based on adverse effects , contra-indications , availability and patient preference : [2]

1-Beta-blockers :

The preferred drug in this class is Labetalol [3]. Metoprolol and pindolol are acceptable alternatives, provided that they are less well-studied In pregnancy [4].

2-Calcium Channel Blockers :

Nifedipine is the most widely used in pregnancy, preferred as intermediate- or extended-release formula [5]. Amlodipine can be used in early pregnancy, since it was not associated with increased risk of fetal malformations [6].

3-Methyldopa :

It is widely used in pregnancy due to its long term safety profile [7] .

4- Hydralazine :

The current available evidence does not support the use of Hydralazine as first line agent due to its adverse effects, reflex tachycardia and peripheral edema. So it’s preferred to be used as add-on therapy [8] .

Table 1 : summary of drugs used in NON-severe GHTN in pregnancy

** Here are some Common anti-hypertensive Drugs to be AVOIDED in pregnancy; due to increased risk of congenital malformations : [9],[10]

ACE inhibitors ( -pril , e.g : enalapril , lisinopril … etc )
ARBs ( -sartan, e.g : valsartan , candesartan … etc )
direct renin inhibitors ( e.g : Aliskiren )
Mineralocorticoid receptor antagonists ( such spironolactone , amiloride )

* First-line Drugs used ACUTELY to treat SEVERE blood pressure elevation in pregnancy ( BP ≥160/110 mmHg ) : [2],[11]

1- Labetalol, IV

2- Nifedipine , Immediate release capsules

3- Hydralazine , IV

Table 2 : summary of drugs used in SEVERE GHTN in pregnancy

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:

[1]- Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020 Jun;135(6):e237-e260. doi: 10.1097/AOG.0000000000003891. PMID: 32443079.

[2]- Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy:

Executive Summary . No. 307, May 2014 . Laura A. Magee, MD, Vancouver BC . Anouk Pels, MSc, Amsterdam, the Netherlands . Michael Helewa, MD, Winnipeg MB . Evelyne Rey, MD, Montreal QC . Peter von Dadelszen, MBChB, Vancouver BC.

[3]- Magee LA; CHIPS Study Group, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Gruslin A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort JW, Welch R, Thornton JG, Moutquin JM. Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial. BJOG. 2016 Jun;123(7):1143-51. doi: 10.1111/1471-0528.13569. Epub 2015 Aug 11. PMID: 26265372.

[4]- Bateman BT, Heide-Jørgensen U, Einarsdóttir K, Engeland A, Furu K, Gissler M, Hernandez-Diaz S, Kieler H, Lahesmaa-Korpinen AM, Mogun H, Nørgaard M, Reutfors J, Selmer R, Huybrechts KF, Zoega H. β-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study. Ann Intern Med. 2018 Nov 20;169(10):665-673. doi: 10.7326/M18-0338. Epub 2018 Oct 16. PMID: 30326014; PMCID: PMC6854680.

[5]- Firoz T, Magee LA, MacDonell K, Payne BA, Gordon R, Vidler M, von Dadelszen P; Community Level Interventions for Pre-eclampsia (CLIP) Working Group. Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review. BJOG. 2014 Sep;121(10):1210-8; discussion 1220. doi: 10.1111/1471-0528.12737. Epub 2014 May 16. PMID: 24832366; PMCID: PMC4282072.

[6]- Mito A, Murashima A, Wada Y, Miyasato-Isoda M, Kamiya CA, Waguri M, Yoshimatsu J, Yakuwa N, Watanabe O, Suzuki T, Arata N, Mikami M, Ito S. Safety of Amlodipine in Early Pregnancy. J Am Heart Assoc. 2019 Aug 6;8(15):e012093. doi: 10.1161/JAHA.119.012093. Epub 2019 Jul 26. PMID: 31345083; PMCID: PMC6761676.

[7]- Magee LA; CHIPS Study Group, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Gruslin A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort JW, Welch R, Thornton JG, Moutquin JM. Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial. BJOG. 2016 Jun;123(7):1143-51. doi: 10.1111/1471-0528.13569. Epub 2015 Aug 11. PMID: 26265372.

[8]- Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003 Oct 25;327(7421):955-60. doi: 10.1136/bmj.327.7421.955. PMID: 14576246; PMCID: PMC259162.

[9]- Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006 Jun 8;354(23):2443-51. doi: 10.1056/NEJMoa055202. PMID: 16760444.

[10]- Hecker A, Hasan SH, Neumann F. Disturbances in sexual differentiation of rat foetuses following spironolactone treatment. Acta Endocrinol (Copenh). 1980 Dec;95(4):540-5. doi: 10.1530/acta.0.0950540. PMID: 7456979.

[11]- ACOG Committee Opinion No. 767: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Obstet Gynecol. 2019 Feb;133(2):e174-e180. doi: 10.1097/AOG.0000000000003075. PMID: 30575639.

Data Science and Coding for Clinicians – Where to Start

August 6, 2021July 29, 2021 Baljash Cheema, MD, MSCI

Medicine is seeing an explosion of data science tools in clinical practice and in the research space. Many academic centers have created institutions tailored to integrating machine learning (ML) and artificial intelligence (AI) into medicine, and major associations including the AHA have created funding opportunities and software tools for clinicians interested in harnessing the promise of big data for their research.

While knowledge on the underlying algorithms and writing code is not necessary to lead a multidisciplinary team working in this space, there are those that want a working knowledge of what is happening under the hood. Thankfully, the computer science (CS) and AI communities have numerous free, online resources to help with this. As I embark on a Masters in Artificial Intelligence, I have used these courses as prep work and found them to be highly educational.

Python for Everybody – By Dr. Charles R. Severance, University of Michigan

This course is meant to get those with no programming background up and running with Python. It focuses on understanding the underlying syntax of the language and the various data structures that come standard in Python. It also touches on web applications, SQL, and data visualization. Thorough, but approachable, this is a great place to start.

CS50x – By Dr. David Malan, Harvard University

One of the most popular courses at Harvard, this course is an intensive introduction to computer science, focusing on key concepts and using various programming languages to illustrate them. The first half or so of the course teaches you to program in C, a low-level language that illustrates how a computer really functions, before moving on to Python (and various Python frameworks), SQL, and web programming. While the juice is definitely worth the squeeze, this course is a commitment and takes significant mental energy to get through.

Machine Learning – By Dr. Andrew Ng, Stanford

One of the courses that popularized the massive open online course (MOOC) revolution, here AI visionary Dr. Ng takes you through a survey of ML/AI algorithms with real world examples and problem sets to work through. The main programming language is MATLAB. This course is enough to give you a basic overview of how these algorithms run and the types of data they are best at handling, serving as a solid introduction to the field.

Machine Learning for Healthcare – By Peter Szolovits and David Sontag, MIT

Healthcare in general and the data it generates is unique, posing challenges distinct from other fields where ML/AI are commonly employed. This course highlights these points through a thorough investigation of healthcare data, common questions clinicians ask in routine patient care, and the clinical integration of ML. It touches on many different topics, including ML for cardiac imaging, natural language processing and clinical notes, and reinforcement learning. No coding is required for this course.

While these courses are just a start, they provide the groundwork for further investigation. in many cases, they are enough to develop an intuition of more complex material including deep learning. If these are topics that interest you, I encourage you to jump on in!

Near the End, and Preparing for a New Beginning

August 2, 2021July 29, 2021 Patrick Tomko

You’ve finally hit that point, where “comps” (comprehensive exams) has been completed. You passed. Now all you have to do is collect data, write it up and present it to your committee. The next challenge is figuring out the time to present the data you collected for the dissertation or thesis. Not to consider the biggest challenge of collecting data that is quality and timely. Thus, there is a few things to consider that might help streamline the PhD journey, or any similar terminal degree.

Thesis/Dissertation Tips

These tips need the context of a “best dissertation/thesis is a done dissertation/thesis”.

Start coming up with ideas for your dissertation/thesis. The ideas evolve, be open to that. Discuss not only with potentially faculty, but also your friends and even family.
Develop a rapport with all the faculty, feel out who may suit you and your journey the best. There is a fit that is needed on both the mentoring and mentee sides of the journey.
Set expectations for yourself and then for your direct report or mentor. This will help ensure efficiency. The mentor has likely been in your shoes before, so he or she may view the initiative and eagerness as a positive.
1. At the same time learn to establish a balance between work and your life. Talk to your mentor about this, he or she likely has valuable input. This is important because the majority of graduate students experiencing anxiety and or depression did not agree with the idea of their advisor being as asset to their career (shown in Figure 1) (Evans et al., 2018).

Figure 1. This figure highlights the graduate students and their experience of depression and anxiety as well as input related to perceived mentorship.
.https://doi.org/10.1038/nbt.4089.

Make sure to back-up all your work. Back it up in more than one spot as well.
It is never too early to start drafting up or writing down and organizing your ideas and concepts.
1. Two sections that you really can get a jump on are the introduction and methods types of sections (Wyllie, 2021).

Future Investigator Tips:

On top of completing the thesis/dissertation, you should really be applying to jobs and considering what would be the next best step for you as a researcher. Dr. Douglas Seals published a very informative manuscript titled “The Academic Biomedical Research Laboratory as a “Small Business”. He provides a perspective that shows biomedical research laboratories providing services to external organizations (Seals, 2021). These services include:

“ -..manuscripts submitted for publication to scientific journals, grant applications submitted to biomedical research funding agencies; and abstracts submitted to professional organizations for presentations” (Seals, 2021).

Dr. Seals viewpoint manuscript is valuable because it highlights the need for developing a network. You learn about the future timelines and the associated potential hurdles. Furthermore, it will help address the a new type of balance, completing the work that you have obtained funding for, and beginning new work from ideas you have formulated. Beyond understanding the dynamics of a laboratory as a small business, developing yourself as a good writer will be something that continues, and a standard that should be set high for yourself.

Find a skill set you would like grow with over time
Look potentially broadening your network.
Understand the importance of treating a lab like a small business.

Below in Figure 2, shows what would be the priorities as a PI through a career. Understanding the frame-work over time can help you determine where you are and where you would like to be as an independent researcher. One of the skills that will need development, will be motivating a variety of people in a variety of ways (Banks, 2021).

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.15755

Finally, do your best to continue to find feedback from quality people with the network you established. Research is a process not only for sample and/or population studied, but for you and your development as an independent investigator. Develop patience and diligence.

Reference

Banks, L. (2021). Words of Advice: How to be a good Principal Investigator. The FEBS Journal, 288(13), 3973–3977. https://doi.org/10.1111/febs.15755

Evans, N. R., Shahrokni, R. O., Ferriday, D., Potter, C., Jebb, S. A., Brunstrom, J. M., & Rogers, P. J. (2018). Enhancing meal enjoyment: Evaluating the effects of flavour intensity and hedonic labelling. Appetite, 130, 304. https://doi.org/10.1016/j.appet.2018.05.184

Seals, D. R. (2021). The Academic Biomedical Research Laboratory as a “Small Business.” Journal of Applied Physiology. https://doi.org/10.1152/japplphysiol.00233.2021

Wyllie, D. J. A. (2021). Thesis write-up and manuscript preparation: Related but distinct tasks. The Journal of Physiology, 599(11), 2771–2775. https://doi.org/10.1113/JP281665

Medications to Avoid in patients with Heart Failure

July 30, 2021July 29, 2021 Lina Ya'qoub, MD

The number of patients being diagnosed with heart failure (HF) is increasing worldwide, and thus we need to know which medications to avoid or be cautious with prescribing that may cause or exacerbate this medical condition. So, we decided to talk about these medications, how they cause these adverse events in these patients, and their mechanism of action.

How these medications cause adverse events in HF patients?

Overall, these medications might cause these adverse effects by one of the following mechanisms: 1) causing direct myocardial toxicity; 2) by negative inotropic effect; 3) chronotropic effects; 4) by exacerbating hypertension; 5) by delivering a high sodium load; or 6) by drug-drug interactions that limit the beneficial effects of HF medications.

Here, we will talk briefly about the common medication classes that should be avoided in heart failure and their mechanism of causing these adverse events.

1. Non-dihydro Calcium Channel Blockers (CCB):

Including (diltiazem and verapamil) è have a negative inotropic effect, thus might increase adverse outcomes [1].

2. Nonsteroidal Anti-Inflammatory Drugs (NSAID) : Diclofenac , indomethacin , ketorolac ..etc AND COX-2 selective inhibitors (Celecoxib) :

Commonly Dispensed as over the counter drugs or as anti-inflammatory prescribed drugs è these medications are associated with increased risk of HF exacerbation, causing decline in renal function, and peripheral vasoconstriction; as such they can attenuate the efficacy and enhance the toxicity of diuretics and angiotensin converting enzyme inhibitors [2].

US Boxed Warning regarding Serious cardiovascular risk: (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use. Celecoxib is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [2].

3. Some Oral Hypoglycemic Agents:

Thiazolidinediones such as Pioglitazone è are associated with fluid retention

US Boxed Warning: Thiazolidinediones may cause or exacerbate heart failure è closely monitor for signs and symptoms of HF particularly after initiation or dose increases. If HF develops, treat and consider dose reduction or discontinuation of pioglitazone. Initiation of therapy is contraindicated in patients with NYHA class III or IV HF [3].

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: Sitagliptin, saxagliptin, and linagliptin

In a scientific statement from American Heart Association (AHA) , saxagliptin has been determined to be an agent that may exacerbate underlying myocardial dysfunction , 2016 . The ADA recommends avoiding the use of saxagliptin in patients with HF, 2020) [4].

Bies ( Metformin ) is associated withguanid lactic acidosis, which can be fatal in patients with CHF

US Boxed Warning regarding Lactic acidosis: Risk factors include renal impairment, ≥65 years and hypoxic states, e.g: acute congestive heart failure. Metformin may be used in patients with stable heart failure, ADA 2020 [5].

4. Tumor Necrosis Factor alpha inhibitors (Anti-TNF-alpha):

Including infliximab, etanercept, and adalimumab.

Use with caution in patients with mild HF (NYHA class I, II) or decreased left ventricular function. Infliximab doses >5 mg/kg are contraindicated with moderate to severe HF (NYHA class III/IV). In a scientific statement from AHA, TNF blockers have been determined to cause either direct myocardial toxicity or exacerbate underlying myocardial dysfunction, 2016 [6,7].

5. Antiarrhythmic medications:

Class I: Flecainide, disopyramide [8]

Class III: Dronedarone, Sotalol [8]

6. Anti- Cancer medications:

Anthracyclines: doxorubicin, Daunorubicin, Mitoxantrone

US Boxed Warning: Myocardial damage (including acute left ventricular failure) can occur with doxorubicin with incidences from 1% to 20% for cumulative doses from 300 mg/m² to 500 mg/m² when administered every 3 weeks è monitor LVEF before, during and after treatment [9]

Targeted therapy: Bevacizumab, Lapatinib, Trastuzumab

US Boxed Warning: Trastuzumab is associated reductions in left ventricular ejection fraction (LVEF) and heart failure; the incidence is highest in patients receiving trastuzumab with an anthracycline-containing chemotherapy regimen è Evaluate LVEF in all patients prior to and during treatment; discontinue for cardiomyopathy [10]

7. Cilostazol

This is a selective inhibitor of phosphodiesterase type 3, antiplatelet and vasodilatory agent used primarily in patients with intermittent claudication and peripheral arterial disease [11].

US Boxed Warning: Cilostazol is contraindicated in patients with heart failure of any severity è causing decreased survival in patients with class III to IV heart failure [11].

8. Anti-depressant drugs:

Citalopram, Tricyclic antidepressants (TCA) such as amitriptyline, Imipramine … etc.

TCAuse with extreme caution in patients with a history of CVD or family history of sudden death, dysrhythmias, or conduction abnormalities. In a scientific statement from AHA, TCA has been determined to exacerbate underlying myocardial dysfunction,2016 è monitor EKG [12]

Citalopram risk of dose-dependent QT prolongation ECG and torsade de pointes (TdP) . Risk factors include Structural heart disease, e.g: MI or HF [12]

9. α1 -Blockers:

Such as prazosin and doxazosin

In a scientific statement from the AHA, -Zosin has been determined to exacerbate underlying myocardial dysfunction , 2016 [13].

10. Pregabalin

Peripheral edema may occur in patients with or without a prior history of heart failure, which may result in acute decompensated heart failure. Risk factors: Pre-existing heart failure (NYHA Class III or IV) (cautious use recommended due to limited data in this patient population [14]

11. Beta-blockers (except those approved for HF treatment: Metoprolol, Bisoprolol, Carvedilol) [15]

12. Selected Intravenous and Oral Medications High in Sodium content:

Oral meds: Alendronate effervescent tablet, Sodium polystyrene sulfonate suspension, Polyethylene glycol powder for solution, erythromycin
Injection meds: Piperacillin/tazobactam, Metronidazole, Ticarcillin/clavulanate, azithromycin

13. Trimethoprim-sulfamethoxazole (TMP/SMX)

==> by increasing the risk of Hyperkalemia which can be life-threatening [16].

Figure 1: Summary of medications to avoid in heart failure patients.
AAA: anti-arrhythmic agents

A special thank you to my sister, Pharm.D Rawan Ya’acoub, Clinical pharmacist and Research assistant at Jordan university .

References:

[1] Kostis JB, Lacy CR, Cosgrove NM, Wilson AC. Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction. Am Heart J. 1997 May;133(5):550-7. doi: 10.1016/s0002-8703(97)70150-9. PMID: 9141377.

[2] Ungprasert P, Srivali N, Kittanamongkolchai W. Non-steroidal anti-inflammatory drugs and risk of heart failure exacerbation: A systematic review and meta-analysis. Eur J Intern Med. 2015 Nov;26(9):685-90. doi: 10.1016/j.ejim.2015.09.012. Epub 2015 Oct 1. PMID: 26427540.

[3] Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care. 2007 Aug;30(8):2148-53. doi: 10.2337/dc07-0141. Epub 2007 May 29. PMID: 17536074.

[4] Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, Udell JA, Mosenzon O, Im K, Umez-Eronini AA, Pollack PS, Hirshberg B, Frederich R, Lewis BS, McGuire DK, Davidson J, Steg PG, Bhatt DL; SAVOR-TIMI 53 Steering Committee and Investigators*. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014 Oct 28;130(18):1579-88. doi: 10.1161/CIRCULATIONAHA.114.010389. Epub 2014 Sep 4. Erratum in: Circulation. 2015 Oct 13;132(15):e198. PMID: 25189213.

[5] Kinsara AJ, Ismail YM. Metformin in heart failure patients. Indian Heart J. 2018 Jan-Feb;70(1):175-176. doi: 10.1016/j.ihj.2017.05.009. Epub 2017 May 15. PMID: 29455774; PMCID: PMC5902828.

[6] Behnam SM, Behnam SE, Koo JY. TNF-alpha inhibitors and congestive heart failure. Skinmed. 2005 Nov-Dec;4(6):363-8. doi: 10.1111/j.1540-9740.2005.04502.x. PMID: 16276152.

[7] Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT; Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003 Jul 1;107(25):3133-40. doi: 10.1161/01.CIR.0000077913.60364.D2. Epub 2003 Jun 9. PMID: 12796126.

[8] Køber L, Torp-Pedersen C, McMurray JJ, Gøtzsche O, Lévy S, Crijns H, Amlie J, Carlsen J; Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008 Jun 19;358(25):2678-87. doi: 10.1056/NEJMoa0800456. Erratum in: N Engl J Med. 2010 Sep 30;363(14):1384. PMID: 18565860.

[9] Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol Lett. 2019 Jun 1;307:41-48. doi: 10.1016/j.toxlet.2019.02.013. Epub 2019 Feb 25. PMID: 30817977.

[10] Nemeth BT, Varga ZV, Wu WJ, Pacher P. Trastuzumab cardiotoxicity: from clinical trials to experimental studies. Br J Pharmacol. 2017 Nov;174(21):3727-3748. doi: 10.1111/bph.13643. Epub 2016 Nov 25. PMID: 27714776; PMCID: PMC5647179.

[11] Wu CK, Lin JW, Wu LC, Chang CH. Risk of Heart Failure Hospitalization Associated With Cilostazol in Diabetes: A Nationwide Case-Crossover Study. Front Pharmacol. 2019 Jan 7;9:1467. doi: 10.3389/fphar.2018.01467. PMID: 30666197; PMCID: PMC6330376

[12] Teply RM, Packard KA, White ND, Hilleman DE, DiNicolantonio JJ. Treatment of Depression in Patients with Concomitant Cardiac Disease. Prog Cardiovasc Dis. 2016 Mar-Apr;58(5):514-28. doi: 10.1016/j.pcad.2015.11.003. Epub 2015 Nov 10. PMID: 26562328.

[13] Hundemer GL, Knoll GA, Petrcich W, Hiremath S, Ruzicka M, Burns KD, Edwards C, Bugeja A, Rhodes E, Sood MM. Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study. Am J Kidney Dis. 2021 Feb;77(2):178-189.e1. doi: 10.1053/j.ajkd.2020.07.018. Epub 2020 Sep 11. PMID: 32920153.

[14] Lund M, Poulsen G, Pasternak B, Worm Andersson N, Melbye M, Svanström H. Use of Pregabalin and Worsening Heart Failure: A Nationwide Cohort Study. Drug Saf. 2020 Oct;43(10):1035-1044. doi: 10.1007/s40264-020-00969-6. PMID: 32651945

[15] Kotecha D, Flather MD, Altman DG, Holmes J, Rosano G, Wikstrand J, Packer M, Coats AJS, Manzano L, Böhm M, van Veldhuisen DJ, Andersson B, Wedel H, von Lueder TG, Rigby AS, Hjalmarson Å, Kjekshus J, Cleland JGF; Beta-Blockers in Heart Failure Collaborative Group. Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure. J Am Coll Cardiol. 2017 Jun 20;69(24):2885-2896. doi: 10.1016/j.jacc.2017.04.001. Epub 2017 Apr 30. PMID: 28467883.

[16] Michel A, Martín-Pérez M, Ruigómez A, García Rodríguez LA. Risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure: a nested case-control study in UK general practice. Eur J Heart Fail. 2015 Feb;17(2):205-13. doi: 10.1002/ejhf.226. Epub 2015 Jan 10. PMID: 25581138.

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

July 23, 2021July 15, 2021 Kyla Lara-Breitinger, MD

“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:

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.

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.

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.

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.

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.

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.

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.