Lina Ya’qoub, MD – The Early Career Voice

Women in Electrophysiology

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

References:

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

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

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

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

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.

“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.”

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.

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.

Diabetic medications with benefit in cardiac patients

July 12, 2021July 7, 2021 Lina Ya'qoub, MD

In the past 1-2 years, strong evidence from randomized clinical trials has shown that certain diabetic medications have benefits in cardiac patients, including improved survival [1-3]. One of these medication classes is Sodium glucose co-transporter 2 (SGLT2) inhibitors. The DAPA-HF trial showed the benefit of Dapagliflozin [1], EMPEROR trial showed the benefit of Empagliflozin [2] and CANVAS trial showed the benefit of Canagliflozin [3]. Long-term pharmacologic therapy in patients with heart failure with reduced ejection fraction and chronic kidney disease has been evaluated and proved to have survival benefits and reduce the disease progression through multiple mechanisms. In this blog, we will discuss some of the SGLT-2 inhibitors data, doses in diabetes and heart failure, and some of their common side effects.

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

Agent name

Dose in heart failure patients

Usual dose for Diabetes Melleitus

Initial eGFR to initiate drug therapy

Side effects

Empagliflozin

10 mg once daily

With/without DM

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

≥45 ml/minute/ 1.73 m²

-Vulvo-vaginal candidiasis

-urinary tract infections

-bone fractures

-thirst and Increased urine out put

– hypovolemia / reduced systolic pressure

-acute kidney injury

-increased risk of lower limb amputation

– DKA

-Necrotizing fasciitis (Fournier gangrene)

– long-term safety not established

Dapagliflozin

10 mg once daily

With/without DM

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

≥45 ml/minute/ 1.73 m²

Canagliflozin

100 mg once daily

With type 2 DM

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

≥30 ml/minute/ 1.73 m²

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

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

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

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

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

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

References:

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

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

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

Summary of COVID-19 Medications

June 28, 2021June 25, 2021 Lina Ya'qoub, MD

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

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

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

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

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

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

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

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

Bamlanivimab-etesevimab
Casirivimab-imdevimab
Sotrovimab

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

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

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

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

Series 1 – Interview with a Pioneer in Humanitarian and Voluntary Work: Dr. Yassine Abdeljebbar

May 12, 2021May 7, 2021 Lina Ya'qoub, MD

I have always been impressed and inspired by the impact of medicine and voluntary work on people’s life. I have recently known about great initiatives and projects organized by young physicians across the globe to help those who are in need. I had the pleasure to interview one of these inspiring physicians, Dr. Yassine Abdeljebbar. I decided to dedicate series of blogs to talk about voluntary and humanitarian work, how to get involved in these projects and how was Dr. Yassine Abdeljebbar’s experience in this field.

It is our pleasure to interview you Dr. Yassine Abdeljebbar!! To start our interview, tell us about yourself and your brief journey.

I am a young doctor, started my career in a public hospital and joined from the beginning of my career the health center located in the Algerian extreme south, In Guezzam more precisely. I came to the United States of America to do research as a postdoctoral fellow at Mount Sinai hospital Icahn school of medicine in 2019.

Originally from west Algeria, since I started studying medicine, I have always tried to put my services to the most disadvantaged, which provided me a rich experience in the charitable field. I am a member of many organizations and medical associations, even environmental ones such as Collective HAMEB, Je Vous Aime, AAMICO, OIM , we Algerians .. etc

Today, I am committed to promoting a positive spirit in the new generations. I aim to inspire the young people who would, in turn, like to become activists by sharing my experience and my passion for mutual aid and solidarity through various humanitarian actions, conferences, workshops, appearances on television, radio, and on social networks.

How did you come up with the idea of devoting yourself to humanitarian work?

The idea of humanitarian work had been around since I was young. As a human, I felt a desire but, above all an immense need to help others. I have never imagined walking my way past someone who needs me without reaching out to him. I dreamed of doing medicine to help those who are suffering because I can understand their struggles. My principle is humanity above all. As a doctor, you should put yourself in the patient’s shoes, sympathize with his pain, and then do everything possible to ease the pain.

Thanks to my parents, I am capable of chairing my passion for charity work today. They encouraged me to study medicine and help people who are in need.

Any advice for doctors or future doctors who want to get into humanitarian work?

Humanitarian work doesn’t just give you moral satisfaction, it’s also a great way to learn medicine in the field, so never hesitate to get involved with others. It’s an excellent experience that will help you and your community.

Stay tuned for more discussions in future blogs!! In future blogs, we will discuss more of these humanitarian activities, share some photos of prior experiences, and share resources for those interested in joining.

I would like to say a special thank you to Dr. Yassine Abdeljebbar, who dedicated the time to interview with us and share his experiences with all of us.

Why Diversity Matters: from a fellow perspective

March 13, 2021March 12, 2021 Lina Ya'qoub, MD

In this blog, I want to share my thoughts on diversity, why it matters in medicine, especially in cardiology.

Why does diversity matter in medicine?

We all are seeing more and more diverse patients, especially in the United States, where “minorities” who come from various backgrounds and cultures constitute a significant proportion of our patients, yet there remain significant disparities across various levels of social life and health care.

Effective Communication

While the language is key in order to provide effective communication between patients and physicians, optimal care should be provided to all patients, irrespective of their origin or language proficiency. Interpreters can help in person or using online resources.

Understanding the Culture

In addition to the language, culture differs significantly between various populations, even those speaking the same language might have different cultures. This is an important part of the patient-physician relationship. One example of how to improve that would be that we try to talk briefly with our patients about their preferences and what is important to them, especially when it comes to goals of care.

Diversity in the Workplace

The importance of culture and diversity in the workplace is tremendous; not only does it add to the various perspective each physician has on the discussion table or their different approaches in taking care of patients, but also it familiarizes our patients with our diverse workforce. With that being said, seeing more women in cardiology, and cardiologists of various backgrounds is crucial to deliver that message.

What are our leading societies doing to promote diversity?

Thankfully, our leading societies, in medicine, cardiology, and other specialties, have recognized the impact of diversity on the workforce and its role in taking care of the growing diverse population we have been seeing. The American Heart Association (AHA) and American College of Cardiology (ACC) among other societies have continued to work relentlessly to advocate for our patients, fight structural racism and health inequity while promoting diversity and inclusion in the cardiology workforce [1,2]. With that being said, having mentors from similar backgrounds helps juniors find role models to look up to, including students, residents, and maybe fellows who have just started their journey and looking for guidance. Talking about my own experience, I have had mentors from various backgrounds, including my background, and this helped me in so many different ways. I do believe our cardiology community has amazing leaders and role models, and together we can make the future brighter for everyone!!

References

AHA website: Diversity and inclusion https://www.heart.org/en/about-us-shared/diversity-inclusion
ACC Diversity and inclusion https://www.acc.org/about-acc/diversity-and-inclusion

It is February again!! The American Heart and Go Red for Women Month!!

February 15, 2021February 15, 2021 Lina Ya'qoub, MD

It is February again of a new year of hope and progress!! Since it is the “The American Heart and Go Red for Women Month”, I would like to talk about the American Heart Association (AHA) GO RED initiative and discuss why heart disease in women is unique, urging my colleagues across the globe to work diligently to ensure optimal health and heart care for everyone, irrespective of their sex or gender.

What is the GO RED initiative and what does it mean?

The GO RED for Women initiative was launched in 2004 by the AHA with the aim to end heart disease and stroke in women worldwide; by increasing awareness of these diseases in women and removing barriers women face to achieve a healthy life.

Here is what GO RED means:

G: GET YOUR NUMBERS

Check your blood pressure and cholesterol level regularly, and early in life if there is a strong family history of heart disease or hypertension.

O: OWN YOUR LIFESTYLE

Encourage healthy lifestyle by stop smoking, losing weight, exercising, and eating healthy.

R: REALIZE YOUR RISK

Know your risk; heart disease is responsible for 1 in every 5 female deaths [1].

E: EDUCATE YOUR FAMILY

Educate your family members and make healthy food choices for you and your family.

D: DON’T BE SILENT

Spread the knowledge that heart disease is No. 1 killer in women [1]. It is also the No. 1 killer of pregnant women per Center for Disease Control and Prevention (CDC) data [2].

Why is heart disease unique in women?

Not only women tend to have atypical symptoms when they present with heart attacks, but also various diseases might behave differently in women potentially leading to differences in outcomes; highlighting the importance of vigilant clinicians in these cases. Women tend to have atypical symptoms when they present with heart attacks; so they tend to have nausea, vomiting, stomach pain, or atypical chest pain, in contrast to the typical exertional chest pain. Moreover, women have differences in their risk factor profile; a recent study has shown that women tend to have a different blood pressure trajectory; with blood pressure elevation starting as early as the third decade of life, and steeper increments of blood pressure over a lifetime compared to men [3]. In addition to the risk factors, there are certain heart conditions that mainly affect women, including spontaneous coronary artery dissections, which is one of the major causes of heart attacks especially in young and pregnant women [3], eclampsia/pre-eclampsia, and peripartum cardiomyopathy, which still carry significant morbidity and mortality [2].

The medical community is still learning about these diseases and the exact mechanism of each condition; urging the need for more research in this area, launching more initiatives to support these projects, similar to the “Research Goes Red” initiative by the AHA, and expanding related sub-specialties like “cardio-obstetrics”, which is a niche subspecialty focused on the care of pregnant women with heart disease.

Although February is the “American Heart and Go Red for Women Month”, we should celebrate women’s heart health every single day by doing our best in our daily clinical practice, increasing awareness of heart disease and risk factors among women, and by working relentlessly to understand the knowledge gaps we have in order to provide better and optimal care for all of our patients.

I would like to say a special thank you to my mom, Laila Abdullah, and my sisters, Rawan, Razan, and Raghad, for their help on this blog and for their continued support.

REFERENCES

[1] Women and Heart Disease: Center for Disease Control and Prevention (CDC): https://www.cdc.gov/heartdisease/women.htm

[2] Center for Disease Control and Prevention (CDC): https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillancesystem.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Freproductivehealth%2Fmaternalinfanthealth%2Fpregnancy-mortality-surveillance-system.htm

[3] Ji H, Kim A, Ebinger JE, Niiranen TJ, Claggett BL, Bairey Merz CN, Cheng S. Sex Differences in Blood Pressure Trajectories Over the Life Course. JAMA Cardiol. 2020 Mar 1;5(3):19-26. doi: 10.1001/jamacardio.2019.5306. Erratum in: JAMA Cardiol. 2020 Mar 1;5(3):364. PMID: 31940010; PMCID: PMC6990675.

[4] Hayes SN, Kim ESH, Saw J, Adlam D, Arslanian-Engoren C, Economy KE, Ganesh SK, Gulati R, Lindsay ME, Mieres JH, Naderi S, Shah S, Thaler DE, Tweet MS, Wood MJ; American Heart Association Council on Peripheral Vascular Disease; Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Genomic and Precision Medicine; and Stroke Council. Spontaneous Coronary Artery Dissection: Current State of the Science: A Scientific Statement From the American Heart Association. Circulation. 2018 May 8;137(19):e523-e557. doi: 10.1161/CIR.0000000000000564. Epub 2018 Feb 22. PMID: 29472380; PMCID: PMC5957087.

Hopes for 2021

January 16, 2021January 14, 2021 Lina Ya'qoub, MD

As 2020 concluded with all of the unprecedented events, with the tragedies people had to suffer and are still suffering from, with all the good and bad, we enter the New Year of 2021 with some hope; hoping for better health, better strategies to combat what we are dealing with in this pandemic, and being more responsible for each other.

COVID-19 Pandemic

COVID-19 pandemic has changed how we live our lives, and the impact of this pandemic will likely last at least a few years, if not more after the pandemic is over. There are a lot of “unknowns” about COVID-19 infection, including the long-term effects of this infection and the effectiveness of some medications, that we will get to encounter and manage in the next several years.

COVID-19 Vaccine

With multiple effective vaccines discovered recently, healthcare workers were given priority to get the vaccine, followed by more vulnerable patients, including the elderly and those with significant comorbidities. The Centers of Disease Control and Prevention (CDC) website provides helpful information on the currently available vaccines in the United States (US), Pfizer, and Moderna, including their storage, preparation, and expected side effects (Link is provided below) [1]. The hope is that by the Spring of 2021, 75% of the population in the United States will be vaccinated. Moreover, efforts by international organizations, including the World Health Organization (WHO), to distribute the vaccine to all countries are ongoing [2].

COVID-19 New Strains

We have seen the discovery of new strains of COVID-19 infection in the United Kingdom and, most recently, the US. These new mutant strains of COVID-19 may not be covered by the available vaccines, as such, the vaccine is an additional layer of protection, with the other protection measures, including social distancing, masks, and hygiene, which may be the most important way to prevent the spread of these new strains at this point of time.

With all that being said, our hopes for a “normal 2021” depend on how we handle the COVID-19 pandemic, we may not see everything going back to normal in 2021, but we can work on making the initial right steps now so that we have less grief, less “loss,” fewer travel restrictions, with healthier and happier upcoming years!!

Special thank you to my sister, Rawan Ya’acoub, an assistant professor of Doctor of Pharmacy/Clinical Pharmacology at the University of Jordan in Amman, Jordan, who helped me write this blog, and for all of her support.

References

S. COVID-19 Vaccine Product Information: https://www.cdc.gov/vaccines/covid-19/info-by-product/index.html
COVID-19 vaccines: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines