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Anti-platelet therapy in STEMI

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:

  1. 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]

  1. 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]

 

  1. 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 )).

  1. Clopidogrel 75 mg daily
  2. Prasugrel 10 mg daily
  3. 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

or

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

 

No

 

 

-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.

 

“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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Drugs in Gestational Hypertension

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.

 

“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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Data Science and Coding for Clinicians – Where to Start

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.

  1. 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.

  1. 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.

  1. 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.

  1. 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!

“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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Near the End, and Preparing for a New Beginning

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”.

  1. 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.
  2. 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.
  3. 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.

  1. Make sure to back-up all your work. Back it up in more than one spot as well.
  2. 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.

  1. Find a skill set you would like grow with over time
  2. Look potentially broadening your network.
  3. 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

“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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Medications to Avoid in patients with Heart Failure

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.

“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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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.”