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The 21-year-old man who survived an acute myocardial infarction

One of the most important things we can do as health-care providers, parents, teachers, caregivers and peers is to successfully recognize and improve the health issues and health outcomes of the teens and young adults. In this blog I’ll share the story of a young man who was seen by my husband in the ED and sparked my interest as a scientist to study the prevalence and clinical profile of myocardial infarction (MI) in young adults in my community.

I encourage you to share this blog with the young adults in your life, as well as parents and caregivers who have teenagers:

Three nights ago as my husband was preparing to sign off his shift in the ED, a 21 years-old man was brought in by the ambulance with a 30-minute history of severe central, crushing pain radiating down to his left arm. The pain was associated with nausea, vomiting, sweating and breathlessness. It was his first time to ever experience a central crushing pain. The man had a history of membranoproliferative glomerulonephritis and was on immunosuppressive therapy. He was also diagnosed with secondary hypertension and was on enalapril and nifedipine. Thankfully, he was in safe hands, the ED team were able to recognize his symptoms and a diagnosis of acute myocardial infarction was made. But, can you imagine how emotionally and physically upsetting this was to himself and his family.

Overview

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Myocardial Infarction (MI) is a lethal manifestation of CAD and can present as sudden death. Although it mainly occurs in patients older than 45 years, young men and women can suffer from myocardial infarction1. Unfortunately, when it happens to young adults, the disease can carry significant psychological impact, financial constraints and morbidity to the patients and their family. The protection being offered by young age is gradually being taken away with the high prevalence of CAD risk factors in these young adults such as obesity, lack of physical activity and smoking. Several studies have described the clinical profile and outcome of young patients with MI and its incidence ranged between 2%-10%. Overall, young patients are more likely to be male, with a history of smoking and hyperlipidemia, however, they were less likely to have other comorbidities and less extensive CAD on coronary angiogram2.

Causes of myocardial infarction in young adults

The causes of myocardial infarction in young adults can be broadly divided into two groups, those with angiographically normal coronary arteries and those with coronary artery disease of varying etiology.

Angiographically “normal” coronary arteries

  • Hypercoagulable state:
    • Nephrotic Syndrome
      • Proteinuria associated with the nephrotic syndrome results in the loss of low molecular weight proteins which alters the concentration and activity of coagulation factors. As a result, factors IX, XI and XII are decreased due to urinary excretion. While the liver tries to compensate for the hypoalbuminaemic state, there is an increased synthesis of factor II, VII, VIII, X, XIII and fibrinogen resulting in raised blood levels3.
    • Antiphospholipid syndrome (Hughes syndrome)
      • Arterial and venous thrombosis is a prominent feature of this syndrome together with antiphospholipid antibodies and miscarriage in pregnancy. The mechanism of thrombosis with this syndrome is complex and not well understood. However, it is plausible that anti-phospholipid antibodies predispose to premature atherosclerosis which increases the risk of infarction with his syndrome4.
    • Coronary artery spasm
      • Coronary artery spasm (CAS) is probably the predominant mechanism for myocardial infarction with the use of cocaine. Cocaine has been associated with angina, myocardial infarction, tachyarrhythmia’s and bradyarrhythmias, sudden cardiac death and myocardial contraction bands, which can possibly act as a substrate for arrhythmias. The cardiac effects of cocaine are mediated through four main pathways
        1. Endothelial dysfunction which predisposes to vasoconstriction and thrombosis.
        2. Promotion of atherosclerosis
        3. Increased myocardial oxygen demand due to an acute rise in systemic blood pressure and heart rate.
        4. Coronary vasoconstriction caused by its α1- adrenergic properties and calcium dependent direct vasoconstriction5.
    • Coronary embolization
      • Coronary artery embolism is a rare cause of acute myocardial infarction (AMI) and the precise diagnosis remains challenging for the interventional cardiologist. The true prevalence of this nonatherosclerotic entity remains vague because of its difficult diagnosis in the acute setting.
    • Myocardial bridging
      • This is a congenital anomaly in which the coronary artery is embedded within the subepicardial myocardium or has a band of myocardium overlying it. This can impede blood flow during systole that can persist during diastole resulting in myocardial ischemia3.

Angiographically abnormal coronary arteries

We know that even angiographically “normal” looking coronary arteries can still have significant atherosclerotic plaque, and not surprisingly, can still result in myocardial infarction. Therefore, the definition of normality is arbitrary and not definite.

  • Accelerated atherosclerosis
    • The true prevalence of advanced coronary atheroma in young adults is not well studies. An autopsy study of 760 victims of accidents, suicide and homicides aged 15-34 years found advanced coronary atheroma in 2% of males aged 15-19 years and none in women. This reveals that being male solemnly is a risk factor for atherosclerosis. Additionally, in the 30-34 age group, about 20% of men and 8% of women had advanced coronary atheroma. It is known that genetic mutation in the low density lipoprotein receptor produces familial hypercholesterolemia, an autosomal dominant disorder characterized by premature atherosclerosis and high serum cholesterol. Various other lipid fractions and hyperhomocysteinaemia are implicated in premature atherosclerosis and MI3.
  • Aneurysm and anomalous origin of arteries dissection
    • Coronary artery aneurysm are congenital or acquired secondary to Kawasaki’s disease in childhood. They have been linked to myocardial infarction in young adults, although the actual mechanism is not well understood.
  • Spontaneous dissection
    • Spontaneous dissection is a condition with great prevalence in women, especially in the peripartum or early postpartum period. However, it is a rare cause of MI6.

 

REFERENCES:

  1. Wong CP, Loh SY, Loh KK, Ong PJ, Foo D, Ho HH. Acute myocardial infarction: Clinical features and outcomes in young adults in Singapore. World J Cardiol. 2012;4(6):206–210. doi:10.4330/wjc.v4.i6.206
  2. Sinha SK, Krishna V, Thakur R, et al. Acute myocardial infarction in very young adults: A clinical presentation, risk factors, hospital outcome index, and their angiographic characteristics in North India-AMIYA Study. ARYA Atheroscler. 2017;13(2):79–87.
  3. Osula S, Bell GM, Hornung RS. Acute myocardial infarction in young adults: causes and management. Postgrad Med J. 2002;78(915):27–30. doi:10.1136/pmj.78.915.27
  4. Turrent-Carriles A, Herrera-Félix JP, Amigo MC. Renal Involvement in Antiphospholipid Syndrome. Front Immunol. 2018;9:1008. Published 2018 May 17. doi:10.3389/fimmu.2018.01008
  5. Hung MJ, Hu P, Hung MY. Coronary artery spasm: review and update. Int J Med Sci. 2014;11(11):1161–1171. Published 2014 Aug 28. doi:10.7150/ijms.9623
  6. Adlam D, Alfonso F, Maas A, Vrints C; Writing Committee. European Society of Cardiology, acute cardiovascular care association, SCAD study group: a position paper on spontaneous coronary artery dissection. Eur Heart J. 2018;39(36):3353–3368. doi:10.1093/eurheartj/ehy080

 

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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The American Heart Association Annual Scientific 2019 Meeting- “An Engaging and Enlightening experience”

The recent American Heart Association Annual Scientific meeting held in Philadelphia, Pennsylvania was filled with many sessions centered around the area of Cardiac Imaging with emerging areas in Nuclear Cardiac imaging,Echocardiography, Cardiac CT as well as Cardiac MRI. There was also the long awaited results of the ISCHEMIA trial. In addition, the Women in Cardiology (WIC)  Committee had several sessions related to professional development including  several networking opportunities with the WIC networking luncheon as well as a networking WIC dinner that was sponsored by the University of Pennsylvania.   In this blog I will discuss several of these highlights.

 

Heart Disease in Women- Focus on Cardiac Imaging

Drs. Viviany Taqueti and Parham Eshtehardi moderated an excellent session on the multimodality assessment of microvascular coronary artery disease (CAD)  in women.

Invasive Assessment of Microvascular Coronary Artery Disease:

During this session Dr. Carl Pepine discussed invasive assessment of microvascular disease in women. He discussed the use of coronary TIMI frame count (cTFC) to predict adverse events in women with symptoms/signs of ischemia with no obstructive coronary artery disease (INOCA).  He discussed the results of a pilot study from the National Heart, Lung and Blood institute ( NHLBI) sponsored Women’s Ischemia Syndrome Evaluation (WISE) which showed that in women with INOCA, resting cTFC provided independent prediction of hospitalization for angina1. He also discussed the pros and cons of the three invasive methods for the assessment of coronary microvascular function: Thermodilution (IMR), Doppler wire (hMR) and Continuous Thermodilution (MVR). IMR being most user friendly of the 3 methods and has also been a method that has been validated against clinical outcomes. IMR is also feasible in every coronary anatomy. However, IMR is adenosine dependent. hMR and MVR both have reasonable reproducibility. hMR has also been validated against clinical outcomes while MVR provides a direct assessment on coronary blood flow and is adenosine free. However, IMR and hMR are dependent on the use of adenosine2. The indications for invasive coronary function testing (CFT) include (a) Evidence of ischemia with persistent chest pain and no obstructive coronary artery disease (CAD) (b) Chest pain refractory to medical management and (c) Preference for definitive diagnosis. Invasive CFT has excellent safety data with <0.6-0.7% serious adverse event rate (coronary dissection, myocardial infarction)3-5. Invasive diagnosis of coronary microvascular disease in women was associated with worse angina  and hospitalization free survival compared to women without evidence of microvascular CAD6.

Role of Positron Emission Tomography (PET) assessment of Microvascular CAD (CMD) in Women:

Dr. Sharmila Dorbala gave an excellent talk on the use of Cardiac PET to assess the presence of CMD with myocardial blood flow and coronary flow reserve assessment with robust evidence data with over 35 years of research data involving over 20,000 patients.  The presence of severely impaired coronary flow reserve (<2.0)  is associated with excess cardiovascular risk in women relative to men referred for coronary angiography7. She had also discussed the evidence showing that CMD diagnosed with PET was associated with an increased risk of heart failure with preserved ejection fraction (HFpEF). The future of myocardial blood flow assessment with Cadmium Zinc Telluride (CZT) SPECT cameras was also discussed. The key points for the diagnosis of CMD with nuclear perfusion imaging are the following:

  • Nuclear stress imaging is required to assess stress myocardial blood flow (MBF) and to assess myocardial flow reserve: stress MBF/rest MBF
  • The stress agent used for assessment of MBF is typically done with vasodilatory agents such as regadenoson, adenosine or dipyridamole. Cold pressor test is usually done in research labs to assess endothelial dysfunction. Exercise MBF is not very feasible.
  • Epicardial CAD has to be excluded
  • CMD is typically defined as MBF <2.

Quantitative Blood Flow assessment with Cardiac MRI (CMR):

Dr. Chiara Bucciarelli-Ducci gave a very informative talk on the use of CMR to assess myocardial blood flow. The general principles of quantification of blood flow requires knowledge of the amount of contrast agent in the myocardium and knowledge of the amount of contrast agent in the blood pool (arterial input function). The challenge in this assessment is the lack of linearity between signal and contrast concentration. The main sources of non-linearity and bias includes spatial signal variations (sensitivity profile of the surface coils), imperfect saturation of magnetization during contrast bolus passage, T2* decay and signal loss by contrast concentration in the blood pool and non-linear signal response (inherent to saturation recovery). Novel CMR techniques such as perfusion mapping and extracellular volume (ECV) assessment were also discussed. The assessment of cardiac perfusion imaging with inline quantitative flow mapping was also discussed, including the fact that this is a fully automated workflow without any user interaction.

 

Artificial Intelligence in Cardiac Imaging with Cardiac CT and Cardiac PET imaging

There was a very innovative session that discussed the use of machine learning and deep learning in FFR Cardiac CT (FFRct)  to improve diagnostic accuracy. Cardiac CTA has been shown to be an established diagnostic tool in clinical practice with FFRct offering functional information for intermediate and severe lesions. FFRct has also showed good correlation with invasive FFR. Machine Learning improves FFR-ct algorithms with improved accuracy, decreased analysis stime, potential to increase the availability of this FFRct technology and potential cost reduction. Deep Learning (DL) in automatic calcium scoring on cardiac CT using paired convolutional neural networks was also discussed. Assessment of ischemic myocardium with Cardiac CTA with DL was also discussed with the use of tissue segmentation and tissue characterization. The use of DL in cardiac PET was also discussed with regards to its utility in cardiovascular event prediction.

 

The ISCHEMIA trial

The long awaited ISCHEMIA trial results were released at the AHA 2019 and my take home points were outlined in my last blog, https://earlycareervoice.professional.heart.org/my-top-10-take-home-points-from-the-ischemia-trial/

ischemia trial

The ISCHEMIA trial is the largest trial studying an invasive versus conservative strategy for patients with stable ischemic heart disease8. The overall conclusions of the ISCHEMIA trial were:an initial invasive strategy compared with an initial conservative strategy did not demonstrate a reduced risk over a median follow up period of 3.3 years with regards to the primary endpoint of cardiovascular death, myocardial infarction, hospitalization for unstable angina and heart failure as well as with regards to the secondary endpoints of cardiovascular death or myocardial infarction. The probability of at least a 10% benefit of an invasive strategy on all cause mortality was < 10, based on pre-specified Bayesian analysis. The ISCHEMIA trial concluded that patients with stable CAD and moderate to severe ischemia had significant durable improvements in angina control and quality of life with an invasive strategy if they had angina occurring daily/weekly or monthly. Shared decision-making should be done to ensure alignment of treatment with patients’ goals and preferences for patients with angina. However, in patients without angina, an invasive strategy led to minimal symptom improvement or quality of life benefits as compared with a conservative strategy.  An early invasive strategy was not associated with a significant reduction in clinical events.

 

Imaging of Valvular Heart Disease

There was also an enlightening session on the role of cardiac imaging in the assessment of tricuspid valvular heart disease with a focus on severe secondary tricuspid regurgitation as well as congenital Ebstein’s anomaly of the tricuspid valve. The preoperative risk factors for significant post op tricuspid regurgitation that were noted were (a) preoperative tricuspid regurgitation of 2+ or more (b) atrial fibrillation and (c) huge left atrium9. Mitral valve surgery as well as double valve surgery including the aortic and mitral valve were associated factors for the development of late significant tricuspid regurgitation after left sided valve surgery10. Mild to moderate progressive functional  tricuspid regurgitation with tricuspid valve annular dilation of >40 mm or > 21 mm/m2 by 2D echocardiography has a class IIa indication for tricuspid valve repair at time of left sided valve surgery. In addition any symptomatic severe functional tricuspid regurgitation at the time of left sided valve surgery has a  class I indication for tricuspid valve repair or replacement11.

Ebstein’s anomaly involving the tricuspid valve accounts for <1% of congenital heart disease. The tricuspid valve malformation is often complex and typically involves the tricuspid valve leaflets, the chordal apparatus and the myocardium  of the right ventricle. The severity of tricuspid valve leaflet displacement on echocardiography has been identified as an independent predictor of cardiac mortality in patients with Ebstein’s anomaly12.

Primary tricuspid regurgitation may also result from lesions of the tricuspid valve apparatus itself such as in endocarditis, congenital disease or from mechanical trauma  to the leaflets, annulus and/or chordae. Echocardiography remains the primary imaging modality to diagnose the etiology and severity of tricuspid valve disease. Features on echocardiography that may indicate significant tricuspid regurgitation includes  tricuspid valve annular dilation of >40 mm or > 21 mm/m2, tethering distance >0.76 cm, tethering area >1.63 cm2 and right ventricular end systolic area of > 20 cm213. However, CMR and Cardiac CT are useful in some cases. CMR is considered the gold standard for the quantification of tricuspid regurgitation, quantification of right ventricular volumes, evaluation of right ventricular function, assessment of fibrosis and occasionally assessment of the etiology. Limitations for CMR includes presence of cardiac devices, arrhythmias, claustrophobia and renal failure (gadolinium). In special situations tricuspid regurgitation can be complex. 3D echocardiography provides useful information and it is sometimes necessary to assess tricuspid regurgitation with multimodality imaging as Cardiac CT can provide information about the anatomical regurgitant orifice area. Additionally, CMR and Cardiac CT can provide information about the dimensions of the tricuspid valve annular diameter, right heart volumes and function as well as vascular assessment13.  In the presence of significant tricuspid regurgitation, tricuspid valve repair should be performed whenever possible.

 

Multimodality imaging of Aortic Diseases

There was also an excellent session dedicated to the multi modality imaging with CT and MRI  of acute and chronic aortic diseases such as aortic intramural hematoma, aortic aneurysms,  aortic dissection and endovascular repair of the aorta (TEVAR) planning for aortic repair. 4D flow MRI was also discussed with regards to TEVAR planning.

With regards to aortic aneurysms, type B aortic dissection should be considered a chronic disease with complex pathophysiology with up to 75% of patients developing an aortic aneurysm14. Hemodynamic forces are believed to play a central role in this pathophysiology.

In the presence of type B intramural hematoma, tiny intimal disruptions/fenestrations (TID) does not confer poor prognosis as the risk of aorta related events are similar when compared to patient without TID. 14% of these patients progress to focal intimal disruption in a recent meta analysis15.  Focal intimal disruptions and ulcer like projections may cause large communications in intramural aortic hematoma with >3mm connection with the aortic lumen and are typically absent on the initial study. Limited intimal tears of the aorta although rare are an unquestionable cause of acute aortic syndromes and is considered a variant of aortic dissection. It is predominantly seen in type A intramural hematoma with an aneurysmal aorta and patients are older than patients with classic aortic dissection. Limited intimal tears can be seen on state of the art CT angiography and 3D volume rendering can make lesions more conspicuous.

 

Quality Cardiac Imaging

The last day of AHA 2019 was kicked off with an inspiring and informative session that discussed Quality in Cardiac Imaging that was led by several leaders in the field which included Dr. Pamela Douglas and Dr. Leslee Shaw. Dr. Ritu Sachdeva discussed strategies to maximize imaging information and outcomes by facilitating implementation by removing barriers and incentivizing schemes. She also discussed designing strategies to keep up with the pace of technology through improving quality, promoting innovation and research and focusing on adequate training in cardiac imaging. It was also mentioned that achieving excellence in imaging has to include collaboration between providers, professional societies, patients, payers and industry. The focus should move from “Volume Driven Healthcare” to “Value Driven Healthcare”.

The future of Cardiac Imaging in a value based healthcare system has to include definitions of the cardiovascular imager of the future, ensure robust innovation and research and maximizing imaging information and improving outcomes. This was outlined in the “Future of Cardiac Imaging Think Tank” article by Dr. Pamela Douglas16.

 

AHA Presidential Address

The AHA Opening session was a very energetic, encouraging and enlightening session. This session was opened by wonderful performances by Broadway’s Hamilton cast of actors.  The Presidential address by Dr. Robert Harrington (Figure 1)  was encouraging as he spoke on the importance of increasing diversity in the cardiology workforce as well as improving gender equality in the cardiology field.

Figure 1 President of the American Heart Association, Dr. Robert Harrington at the American Heart Association 2019 Annual Scientific Session Presidential Address

Figure 1 President of the American Heart Association, Dr. Robert Harrington at the American Heart Association 2019 Annual Scientific Session Presidential Address

 

AHA Women in Cardiology (WIC) Committee Events

  • Professional Development: There were many Women in Cardiology Professional Development sessions that covered a wide range of topics such as “Volunteerism to Advance Your Career” with Drs. Stacy Rosen and Michelle Albert, “Negotiations” with Drs. Sandra Lewis and Linda GIllam, “Time Management” with Drs. Toniya Singh and Gina Lundberg, “Self-Advocacy” with Drs. Elaine Tseng and Linda Shore, “Sponsor vs. Mentor” with Dr.  Emelia Benjamin and “Around the World with Go Red for Women”. These sessions were held in the Women in Science and Medicine Lounge in the expo hall and were very engaging and well attended sessions.

 

Networking Activities

WIC Networking Luncheon:

The AHA Women in Cardiology networking luncheon was an excellent session that provided an opportunity to network with other colleagues and AHA leadership. This session also hosted an excellent panel of speakers led by Dr. Laxmi Mehta who spoke on the topic of “Physician Burnout” and how to address this issue in Medicine. The other panel of speakers included Dr. Minnow Walsh who discussed the “Increased demand of the aging population and decreased supply of clinicians causing burnout – what can be done?”, Dr. Athena Poppas discussed “What can Cardiology leaders and Chiefs of Cardiology do to help decrease the stress from the clinical workload and increase career satisfaction?”, Dr. Sandy Lewis discussed “Legislative advocacy to decrease physician burnout​ – what can organizations do?” and Dr. Sherry Ann Brown discussed “What can cardiologists do to decrease their stress levels?” and she also discussed “What can fellowship program directors do to help fellows decrease burnout?” The attendees at the luncheon also added their own experiences relevant to this topic and also shared words of wisdom and advice.

The All Council Reception and Clinical Cardiology Council Dinner:

The All Council reception was very well attended with standing room only. It was also very lively with performance by the members from the Mummers Philadelphia group. This reception led into the Clinical Cardiology Council Dinner and during the dinner there were several awards given as well as recognition of the new Fellows of the American Heart Association. Dr. Sharon Reimold was the recipient of the AHA Women in Cardiology Mentoring Award.

The AHA WIC Networking dinner hosted by University of Pennsylvania:

The AHA Women in Cardiology committee was very grateful to the University of Pennsylvania led by Dr. Monika Sanghavi  who hosted a wonderful dinner that provided an opportunity for Women in Cardiology fellows in training (FIT) to network with several Women in Cardiology leaders in the field. We appreciated pearls of wisdom from leaders such as  Dr. Nanette Wenger, Dr. Sharonne Hayes, Dr. Minnow Walsh, Dr. Andrea Russo, Dr. Martha Gulati and Dr. Annabelle Volgmann. This was the second annual WIC event at the AHA Scientific meeting and we are hoping to continue this at future AHA Scientific meetings as these events have been very well received by our Women in Cardiology FITs.

 

AHA 2019 was an educational, engaging and exciting meeting where new scientific data relevant to Cardiology practice was presented. The event also offered many opportunities for networking with many leaders in the field. I look forward to the American Heart Association Scientific meeting in November 2020 in the beautiful city of  Dallas, Texas.

 

References:

  1. Petersen JW, Johnson BD, Kip KE, Anderson RD, Handberg EM, et al. (2014) TIMI Frame Count and Adverse Events in Women with No Obstructive Coronary Disease: A Pilot Study from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE). PLoS ONE 9(5): e96630. doi:10.1371/journal.pone. 0096630
  2. Banning AP, De Maria GL.Measuring coronary microvascular function: is it finally ready for prime time? Eur Heart J. 2019 Jul 21;40(28):2360-2362. doi: 10.1093/eurheartj/ehz426. No abstract available. PMID: 31236565
  3. Wei J, Mehta PK, Johnson BD, Samuels B, Kar S, Anderson RD, Azarbal B, Petersen J, Sharaf B, Handberg E, Shufelt C, Kothawade K, Sopko G, Lerman A, Shaw L, Kelsey SF, Pepine CJ, Merz CN.Safety of coronary reactivity testing in women with no obstructive coronary artery disease: results from the NHLBI-sponsored WISE (Women’s Ischemia Syndrome Evaluation) study. JACC Cardiovasc Interv. 2012 Jun;5(6):646-53. doi: 10.1016/j.jcin.2012.01.023.PMID: 22721660
  4. Reriani M, Sara JD, Flammer AJ, Gulati R, Li J, Rihal C, Lennon R, Lerman LO, Lerman A.Coronary endothelial function testing provides superior discrimination compared with standard clinical risk scoring in prediction of cardiovascular events. Coron Artery Dis. 2016 May;27(3):213-20. doi: 10.1097/MCA.0000000000000347. PMID: 26882018
  5. Ong P, Athanasiadis A, Borgulya G, Vokshi I, Bastiaenen R, Kubik S, Hill S, Schäufele T, Mahrholdt H, Kaski JC, Sechtem U. Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation. 2014 Apr 29;129(17):1723-30. doi: 10.1161/CIRCULATIONAHA.113.004096. Epub 2014 Feb 26. PMID: 24573349
  6. AlBadri A, Bairey Merz CN, Johnson BD, Wei J, Mehta PK, Cook-Wiens G, Reis SE, Kelsey SF, Bittner V, Sopko G, Shaw LJ, Pepine CJ, Ahmed B. Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women. J Am Coll Cardiol. 2019 Feb 19;73(6):684-693. doi: 10.1016/j.jacc.2018.11.040. PMID: 30765035
  7. Taqueti VR, Shaw LJ, Cook NR, Murthy VL, Shah NR, Foster CR, Hainer J, Blankstein R, Dorbala S, Di Carli MF. Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease.’Circulation. 2017 Feb 7;135(6):566-577. Doi: 10.1161/CIRCULATIONAHA.116.023266. Epub 2016 Nov 14.PMID: 27881570
  8. https://www.google.com/url?q=http://www.ischemiatrial.org/&sa=D&ust=1576542824370000&usg=AFQjCNH06i1Ohvx0btiCyHrVJARGarMYOA
  9. Matsuyama K, Matsumoto M, Sugita T, Nishizawa J, Tokuda Y, Matsuo T. Predictors of residual tricuspid regurgitation after mitral valve surgery. Ann Thorac Surg. 2003 Jun;75(6):1826-8. PMID: 12822623
  10. Song H, Kim MJ, Chung CH, Choo SJ, Song MG, Song JM, Kang DH, Lee JW, Song JK.
    Factors associated with development of late significant tricuspid regurgitation after successful left-sided valve surgery. Heart. 2009 Jun;95(11):931-6. doi: 10.1136/hrt.2008.152793. Epub 2009 Mar 24. PMID: 19321491
  11. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD; ACC/AHA Task Force Members.2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation. 2014 Jun 10;129(23):e521-643. doi: 10.1161/CIR.0000000000000031. Epub 2014 Mar 3.
  12. Tobler D, et al. Tricuspid Valve Abnormalities. Congenital Heart Diseases in Adults Imaging and Diagnosis. Springer er. 2019
  13. Hahn RT, Thomas JD, Khalique OK, Cavalcante JL, Praz F, Zoghbi WA. Imaging Assessment of Tricuspid Regurgitation Severity. JACC Cardiovasc Imaging. 2019 Mar;12(3):469-490. doi: 10.1016/j.jcmg.2018.07.033. Review. PMID: 30846122
  14. Fattori R, Montgomery D, Lovato L, Kische S, Di Eusanio M, Ince H, Eagle KA, Isselbacher EM, Nienaber CA. Survival after endovascular therapy in patients with type B aortic dissection: a report from the International Registry of Acute Aortic Dissection (IRAD). JACC Cardiovasc Interv. 2013 Aug;6(8):876-82. doi: 10.1016/j.jcin.2013.05.003. PMID: 23968705
  15. Moral S, Cuéllar H, Avegliano G, Ballesteros E, Salcedo MT, Ferreira-González I, García-Dorado D, Evangelista A. Clinical Implications of Focal Intimal Disruption in Patients With Type B Intramural Hematoma. J Am Coll Cardiol. 2017 Jan 3;69(1):28-39. doi: 10.1016/j.jacc.2016.10.045. PMID: 28057247
  16. Douglas PS, Cerqueira MD, Berman DS, Chinnaiyan K, Cohen MS, Lundbye JB, Patel RA, Sengupta PP, Soman P, Weissman NJ, Wong TC; ACC Cardiovascular Imaging Council. The Future of Cardiac Imaging: a Report of a Think Tank Convened by the American College of Cardiology. JACC Cardiovasc Imaging. 2016 Oct;9(10):1211-1223. Doi: 10.1016/j.jcmg.2016.02.027. Review. PMID: 27712724

 

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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AHA19 Reflection

“Half of what we will teach you in medical school is right, and half of it is wrong – the problem is we don’t know which is which.” This quote, or some variation of it, is relayed by many educators at medical schools across the globe. At AHA19, these words rang in my ears as my head was spinning from attending lecture after lecture being given by experts in the field of cardiology. What I found to be most educational (and hilarious), were the debates on controversial topics.

The debates I attended ranged from the age-old IABP vs impella in cardiogenic shock patients, to thought-provoking jabs at conventional practice, such as whether or not sodium restriction is necessary in acute decompensations of heart failure. However, I’m not here to convince you that one form of mechanical circulatory support is superior to another, or that perhaps some of the things we put a lot of stake in (hello salt restriction), might not be true in all cases.

With each debate, when a physician explained their reasoning for being Pro-X or Anti-Y, I couldn’t stop nodding in agreement. Gaining insight into their reasoning was thought provoking in and of itself! I found myself agreeing, disagreeing, and scratching my head at different concepts. It helped me discover gaps within my own knowledge, and pushed me to review the primary literature in a way that no amount of pimping on the wards ever could.

One of my favorite debates was watching Dr. Gregg Stone debate with Dr. Obadia on the merits of mitral valve clipping for secondary mitral regurgitation (the lead investigators of 2 separate trials that basically showed totally different results). Neither physician said the other was wrong! In fact, they both more or less agreed with one another, and helped highlight key differences that a discerning physician should look for when faced with such discrepancies.

And the lectures that weren’t meant to be debates ended up sparking hot debates anyways! I’m looking at you #ISCHEMIA trial. The #Cardiotwitter explosion that began that ensued has been so eye-opening to me as a trainee. Not only did it help highlight some details of landmark trials I might have missed, but it gave me a great window into the line of thought of many skilled clinicians.

Coming through college, medical school, and residency, I’ve been exposed to many different styles of teaching, and I’ve seen conventional medical education evolve from a bunch of disjointed sciences taught in school to a formal systems-based curriculum. Social media has changed the landscape of many fields, and medical education is not immune to its effects. FOAMed (Free open access medical education) and social media have become staples in how some trainees learn, and we must embrace that. The way that the AHA sought to integrate this into their programming was a great experience that truly helped to cement new knowledge for me, and ultimately improve my patients’ care. And as I’ve come to learn, when it comes to these debates, it’s not about who is right or wrong, it’s about how much you can learn form hearing both perspectives.

 

 

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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The Electrocardiogram In The Age of Artificial Intelligence: Decoding Hidden Secrets With Deep Learning

The electrocardiogram (ECG) is arguably the cardiologist’s best friend. Willem Einthoven’s invention created one of the most widely used diagnostic tests in clinical practice. The ECG is an easily available, patient-friendly, noninvasive, inexpensive, and reproducible technique, without peer for the diagnosis of myocardial ischemia, cardiac arrhythmias, structural changes of the myocardium, drug effects, and electrolyte and metabolic disturbances.1 In addition to this, the ECG can provide information about the extent and severity of ischemia in acute coronary syndromes, assist in the localization of the site or pathway for tachycardias, identify heart failure patients who would benefit from cardiac resynchronization and identify familial diseases with risk of sudden cardiac death.

The ECG detects pathological changes prior to the development of structural changes in the heart. For instance, a strain pattern, defined as a down-sloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V5 or V6, is predictive of future risk of HF and death in hypertensive patients.2 In fact, the 12 lead surface ECG is but one format to represent the electrical activity of the heart. Small changes in the morphology of the surface ECG, not visible to the human eye may reflect significant shifts in electrochemical messaging. Techniques such as signal averaged ECG, vectorcardiography aim to overcome these limitations and have been around for several decades.3 However, sophisticated and more advanced applications of the ECG have not found their way into the routine practice of clinical cardiology. Most of these are limited by low sensitivity which prohibits widespread application.

With advances in computational techniques and availability of big data collected from a variety of sources, there have been advances in unpacking the information encoded in several biologic signals. Deep learning is a type of machine learning technique with a diverse set of validated applications such as facial and speech recognition. Using deep learning to analyze retinal fundus images, Google has developed an algorithm that makes a diagnosis of diabetic retinopathy with a high degree of accuracy comparable to ophthalmologists.4 Furthermore, this algorithm detects cardiovascular events and even identifies gender from retinal images alone.5 This work represents a new way of scientific discovery, an alternative to the traditional hypothesis driven research approach. A data-driven approach can help generate newer hypothesis-guided experiments.

Deep learning for the analysis of ECG signals is an area of active research. Hannun and colleagues have shown comparable accuracy and even higher sensitivity for classifying arrhythmias using a deep neural network model versus board certified cardiologists.6 Work presented at scientific sessions 2019 from the University of Dusseldorf by Makimoto and colleagues showed that a convolutional neural network (CNN) was able to diagnose myocardial infarctions (MI) with more accuracy than cardiologists.7 The accuracy of MI recognition in ECGs by CNN was 84±2%, which was significantly higher than by cardiologists (64±7%, p<0.001). Designing clinical workflows where deep learning models provide rapid, expert level over read of ECGs, complemented by human oversight can have significant clinical impact.

The ECG signal represents the various electrical, chemical and mechanical events during the cardiac cycle. Deep learning algorithms have been able to decode these signals to make predictions about LVEF and diastolic dysfunction based on ECG data alone. Sengupta and colleagues used continuous wavelet transformation for post-processing the ECG signals and correlated several derived features for predicting abnormal myocardial relaxation as defined by abnormal tissue doppler.8 The area under the curve for their machine learning model for prediction of abnormal myocardial mechanical relaxation was 91% [CI: 0.86-0.95]. Attia and colleagues from Mayo Clinic presented their work at scientific sessions 2019 on predicting LVEF using single lead ECG signals acquired by an ECG-enabled stethoscope.9 A neural network previously used on 12-lead ECG for predicting EF was trained on single lead ECG data and was able to predict low EF with an area under the curve of 0.88 [CI:0.80-0.94] for EF<=35% and 0.81 [CI:0.72-0.88] for EF<50%

These findings and many others are constantly expanding the utility of the ECG in clinical practice wherein, the ECG provides more nuanced and finer details such as ejection fraction and predicts future outcomes with high accuracy. This represents significant progress from the days of the string galvanometer of Einthoven. Modern cardiovascular medicine is faced with many challenges related to prevention, diagnosis and treatment of disease, compounded by rising healthcare costs. The inexpensive and reliable best friend of the cardiologist – the ECG – can reveal its secrets to tackle these problems. The words of Einthoven remind us that there remains much to be done for decoding these secrets, “An instrument takes its true value not so much from the work it possibly might do but from the work it really does.”10 Future research is needed to validate the promise of these exciting new findings.

 

References:

  1. Wellens HJ, Gorgels AP. The electrocardiogram 102 years after einthoven. Circulation. 2004;109:562-564
  2. Okin PM, Devereux RB, Nieminen MS, Jern S, Oikarinen L, Viitasalo M, Toivonen L, Kjeldsen SE, Dahlof B, Investigators LS. Electrocardiographic strain pattern and prediction of new-onset congestive heart failure in hypertensive patients: The losartan intervention for endpoint reduction in hypertension (life) study. Circulation. 2006;113:67-73
  3. Gatzoulis KA, Arsenos P, Trachanas K, Dilaveris P, Antoniou C, Tsiachris D, Sideris S, Kolettis TM, Tousoulis D. Signal-averaged electrocardiography: Past, present, and future. J Arrhythm. 2018;34:222-229
  4. Gulshan V, Peng L, Coram M, Stumpe MC, Wu D, Narayanaswamy A, Venugopalan S, Widner K, Madams T, Cuadros J, Kim R, Raman R, Nelson PC, Mega JL, Webster DR. Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA. 2016;316:2402-2410
  5. Poplin R, Varadarajan AV, Blumer K, Liu Y, McConnell MV, Corrado GS, Peng L, Webster DR. Prediction of cardiovascular risk factors from retinal fundus photographs via deep learning. Nat Biomed Eng. 2018;2:158-164
  6. Hannun AY, Rajpurkar P, Haghpanahi M, Tison GH, Bourn C, Turakhia MP, Ng AY. Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network. Nat. Med. 2019;25:65-+
  7. Makimoto H, Hoeckmann M, Gerguri S, Clasen L, Schmidt J, Assadi-Schmidt A, Bejinariu A, Mueller P, Gloeckner D, Angendohr S, Brinkmeyer C, Kelm M. Abstract 13914: Artificial intelligence finds myocardial infaction in ecg more accurately than cardiologists. Circulation. 2019;140:A13914-A13914
  8. Sengupta PP, Kulkarni H, Narula J. Prediction of abnormal myocardial relaxation from signal processed surface ecg. J Am Coll Cardiol. 2018;71:1650-1660
  9. Attia ZI, Dugan J, Maidens J, Rideout A, Lopez-Jimenez F, Noseworthy PA, Asirvatham S, Pellikka PA, Ladewig DJ, Satam G, Pham S, Venkatraman S, Friedman P, Kapa S. Abstract 13447: Prospective analysis of utility of signals from an ecg-enabled stethoscope to automatically detect a low ejection fraction using neural network techniques trained from the standard 12-lead ecg. Circulation. 2019;140:A13447-A13447
  10. Rosen MR. The electrocardiogram 100 years later: Electrical insights into molecular messages. Circulation. 2002;106:2173-2179

 

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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AHA19 ….Jaguar, Mustang, Camry

AHA19 Scientific Sessions came to an end last month and we all went back to our homes, but the discussions continued, especially concerning the ISCHEMIA Trial. The study design was very simple (Figure 1). This is a randomized parallel study of patients with stable coronary artery disease and moderate to severe ischemia. Ischemia was defined as ≥10% ischemia on nuclear imaging; ≥3 segments of ischemia by echography; ≥12% ischemia and/or ≥3 segments with ischemia by cardiac magnetic resonance; and ≥1.5 mm ST depression in ≥2 leads or ≥2 mm ST depression in single lead at <7 METs with angina on exercise treadmill testing. Initially, critical anatomy was ruled out by a Coronary Computed Tomography (CCT) ie Left Main disease ≥50%. Then patients were randomized to a routine invasive strategy on top of medical therapy (n = 2,588) versus medical therapy alone (n = 2,591). In the invasive therapy arm, revascularization was either surgical or percutaneous. In the medical therapy arm, angiography was performed if medical therapy failed. Coronary revascularization was performed in 80% of the invasive arm and 23% of the medical therapy arm.  A total of 5179 patients were enrolled and followed up for a duration of 3.3 years. The primary endpoint (cardiovascular (CV) death, myocardial infarction (MI), resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure) occurred in 13.3% of the invasive arm and 15.5% of the medical therapy arm. The secondary endpoints were also similar in both groups (CV death or MI was 11.7% and 13.9% and all-cause death was 6.4% and 6.5% of the invasive and medical therapy arms respectively). The hazard ratio for the periprocedural MI invasive/conservative was 2.98, 95% confidence interval (CI)1.87-4.74 and for the spontaneous MI was invasive/conservative 0.67, 95% CI 0.53-0.83).

The conclusion of the trial is that a routine invasive approach to patients with stable disease and moderate to severe ischemia failed to reduce major adverse cardiac events compared with optimal medical therapy alone.

So, if the results are so definitive why are the discussions and debates on going? Well it’s like car shopping. It’s not just about the color…do I want a sedan?..Is an electric car available in our area?..what is my budget?..Jaguar, Mustang, Camry.

Decisions are tailored to individual patients, individual centers, and individual healthcare systems. If a patient has stable disease with a depressed systolic function, ISCHEMIA is not applicable as a left ventricular ejection fraction <35% was an exclusion criterion as was advanced kidney disease with an estimated glomerular filtration rate <30 ml/min, prior CABG, and New York Heart Association class III-IV heart failure. Centers that don’t have a robust CCT program cannot use the ISCHEMIA protocol to screen patients with angina. Then there are those with occupational dilemmas, especially pilots and military personnel. Will a CCT to rule out left main disease be sufficient or will this pilot remain grounded until an invasive procedure is performed? Will the patient’s insurance cover a CCT, nuclear stress test and then possibly a coronary angiogram?

Presentations of landmark trials at conferences such as AHA ignite discussions that directly impact patient care, guidelines and future trials. The discussions drive the field forward. For interventional cardiologists, these discussions allow for much needed introspection. Unlike many other fields, interventional cardiology has always paved the road to randomized trials that on many occasions limit the inappropriate use eg COURAGE, ORBITA, and now ISCHEMIA. This is what distinguishes this subspecialty from many others.

Figure 1: ISCHEMIA Trial Design

ISCHEMIA Trial Design

  • Average Follow up 3.5 years
  • Primary Endpoints: CV death, MI, resuscitated cardiac arrest, hospitalization for unstable angina or heart failure
  • Secondary Endpoints: CV death, MI, angina QOL

 

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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Is Old Really Gold? The Case Against Aspirin

The recently concluded AHA Scientific Sessions provided for a myriad of sessions on antiplatelet therapy in cardiovascular disease (CVD).

The late-breaking TWILIGHT ACS trial reported a win for ticagrelor monotherapy among patients randomized after 3 months post-NSTE-ACS and PCI, in results consistent with the main TWILIGHT trial.1-2 TWILIGHT ACS showed a reduction of clinically significant bleeding with no increased risk of ischemic adverse events at 1 year, for those randomized to ticagrelor monotherapy versus aspirin plus ticagrelor (DAPT).1

That same day, an entire session aptly titled “Aspirin: who needs it anymore?” dedicated to the dissection of aspirin, featured a series of talks on the role for aspirin for the primary and secondary prevention of cardiovascular disease (CVD).

Questioning the potential “twilight” of aspirin therapy, Dr Roxana Mehran raised some pertinent issues particularly pertaining to bleeding risk and gastrotoxicity of aspirin, in addition to treatment failure/ “aspirin resistance” resulting from its enteric-coated preparation and potential drug-drug interactions.

Nevertheless, while aspirin may still remain in the game with respect to secondary prevention, 3 randomized clinical trials in primary prevention have ensured a “three strikes and you’re out” scenario for aspirin, culminating in a de-emphasis in the guidelines as well.

One of the best things about attending meetings is the effortless re-cap/ additional reading one does afterwards. Thus, in order to discern how such a fate befell aspirin, here’s a brief look at the “three A’s” of 2018 responsible for hitting the nail in the coffin:

 

The ARRIVE (Aspirin to Reduce Risks of Initial Vascular Events) trial

ARRIVE enrolled 12 546 patients (men ≥ 55 years with 2-4 risk factors and women ≥ 60 years with ≥risk factors for CVD) who were randomized to enteric-coated (EC) aspirin 100 mg/day versus placebo.3 ~29·5% of participants were women. Individuals with diabetes and those at high risk of bleeding were excluded. The primary endpoint was a composite outcome of time to first occurrence of CV death, MI, unstable angina, stroke, or transient ischemic attack.

After a median follow-up of 5 years, no significant differences were observed in the primary end-point between those assigned to aspirin vs placebo (4.29% vs 4.48%; p=0.6038), although the event rate was much lower than expected, thus making the study more representative of a low-risk population. The overall incidence of adverse events was similar in both groups, however, there were significantly more gastrointestinal bleeding events (predominantly mild) in the aspirin group than placebo (0.97% vs 0.46%; p=0·0007).

 

The ASPREE (Aspirin in Reducing Events in the Elderly) trial

This trial enrolled 19,114 healthy community-dwelling individuals across sites in Australia and the USA aged ≥ 70 years (or ≥ 65 years if  Black/ Hispanic in US) and devoid of CVD, dementia or disability who were randomized to 100 mg EC aspirin vs placebo.4-6

The primary end-point was a composite of death, dementia or persistent physical disability while secondary end points included major hemorrhage and cardiovascular disease (defined as any ischaemic event).4-6 At 56.4%, ASPREE enrolled the highest number of women from among the three trials.4 The median age of participants was 74 years.

The trial was terminated early at a median of 4.7 years of follow-up, as it was determined that no benefit would be derived with continued aspirin use in terms of primary end point. Accordingly, there were no significant differences in the primary composite outcomes (21.5 vs. 21.2 events per 1000 person-years; p = 0.79 ).4 However, rates of major bleeding were significantly higher in the aspirin group (8.6 vs. 6.2 events per 1000 person-years; p < 0.001),  with a progressive increase in the cumulative incidence of major hemorrhage across the follow-up period.5 The majority of these episodes were gastrointestinal bleeds, with the higher risk of upper GI bleeds being particularly more pronounced with aspirin (hazard ratio, 1.87; 95% CI, 1.32 to 2.66).5

There was also an increased risk of all-cause mortality in the aspirin group versus placebo (12.7 vs 11.1 events per 1000 person-years; HR, 1.14; 95% CI, 1.01 to 1.29) with cancer being the major contributor to the higher mortality seen with aspirin.6 Thus, ASPREE concluded that the daily use of low-dose aspirin did not prolong disability-free survival among the elderly.6

 

The ASCEND (A Study of Cardiovascular Events in Diabetes) trial

A trial specifically designed to investigate the effects of aspirin in primary prevention among diabetics, ASCEND enrolled 15,480 individuals (~37. 5% women) in the United Kingdom with diabetes but no evident CVD who were randomized to 100 mg of aspirin daily versus placebo.7

During a mean follow-up of 7.4 years, those randomized to aspirin had a significantly lower percentage of serious vascular events in comparison to placebo (8.5% vs. 9.6%; P=0.01). However, this benefit was offset by significantly higher major bleeding events seen in the aspirin arm (4.1% vs. 3.2%, p=0.003), with no attenuation of the effect on bleeding over time. As with ARRIVE, the majority (41.3%) of major bleeding events were gastrointestinal, of which close to two thirds were in the upper GI tract. Thus, the trial concluded that the absolute benefits of aspirin in preventing CVD among diabetics were largely counterbalanced by the hazards of bleeding.

These trials formed the basis for the de-emphasis of aspirin in the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, which recommended against the prophylactic use of aspirin among elderly (>70 years) and those at high bleeding risk. There was also a downgrade in class of recommendation for low dose aspirin for primary prevention in select 40 to 70 year-old adults at higher ASCVD risk but lower bleeding risk (Class II b).8

To add to this, a comprehensive meta-analysis of 13 trials comprising of 164 225 participants without cardiovascular disease by Zheng et al., found that aspirin use was associated with a significant reduction of cardiovascular events but also an increased risk of major bleeding events compared with no aspirin.9

As Dr Erin Michos, one of the co-authors of the Primary Prevention guidelines pointed out in her talk at AHA 2019, this poor performance of aspirin in terms of risk-benefit could be attributed to the improved adherence to other primary prevention methods, such a reduction of smoking, better control of blood pressure and importantly more aggressive lipids control by virtue of statins.

With the much-needed emphasis on bleeding and its detrimental effects, “less is more” has been the focus in recent times, at least for antiplatelet and antithrombotic drugs, with recognition of trials that withdraw rather than add to current drug treatments. Furthermore, the appropriate prescription of drugs and increased emphasis on lifestyle modification for primary prevention cannot be understated. The onus is on physicians to keep up to date and tailor drug prescriptions to the individual patient.

Also, in keeping with the spirit of on post-conference re-caps, highly recommend the following as additional reading:

  1. Marquis-Gravel G, Roe MT, Harrington RA, et al. Revisiting the Role of Aspirin for the Primary Prevention of Cardiovascular Disease. Circulation 2019;140(13):1115-1124.
  2. Ridker PM. Should Aspirin Be Used for Primary Prevention in the Post-Statin Era? N Engl J Med 2018;379(16):1572-1574.
  3. Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-60.

References:

  1. Presented by Dr. Usman Baber at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 17, 2019.
  2. Mehran R, Baber U, Sharma SK, et al. Ticagrelor With or Without Aspirin in High-Risk Patients After PCI. N Engl J Med2019;381:2032-42
  3. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet2018;392:1036-46.
  4. McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med 2018;379:1499-1508.
  5. McNeil JJ, Wolfe R, Woods RL, et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med 2018;379:1509-18.
  6. McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med 2018;379:1519-28.
  7. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med 2018;379:1529-39.
  8. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140(11):e596-e646.
  9. Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis. JAMA 2019;321(3):277-287.

 

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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Sensing oxygen – Leland Clark and the origins of direct oxygen measurement in blood

As we’ve all been back from AHA19 for a few weeks now, I began thinking about the research presented. Throughout the conference I tried to focus on topics of aging and cardiovascular disease, which is my current research focus. I kept finding myself in front of posters or at talks on metabolism and my personal favorite organelle, the mitochondria.

I’ve been fascinated by mitochondria since graduate school where I ran ~300 Seahorse assays on clinical samples among other mitochondrial measures. To be clear, I was a bit burnt out on the Seahorse after my PhD but that feeling has faded. These oxygen consumption assays to measure mitochondrial function have gained popularity in recent years, which got me thinking about the origins of these devices.

The first measures of oxygen tension in blood were developed by Leland Clark1. A major limitation of measuring oxygen tension in solutions was that the liquid needed to either be quiescent or constantly stirred, which limited the use in vivo1.

Dr. Leland Clark

Dr. Leland Clark2 (https://en.wikipedia.org/wiki/Leland_Clark#/media/File:Dr._Leland_C._Clark_Jr_2005.jpg)

Measurements I blood, which would be clinically useful, were difficult because tissues were constantly moving. Leland Clark overcame this by developing the polarographic electrode, now termed the Clark Electrode1. This became the foundation for measures of oxygen consumption rate that is the gold standard measure of mitochondrial function in isolated tissue. These are now used in the Seahorse respirometer and the Oroboros oxygraph, the 2 most popular commercial respirometers.

Polarographic oxygen electrode

Polarographic oxygen electrode1 (https://www.physiology.org/doi/pdf/10.1152/jappl.1953.6.3.189)

The development of the Clark Electrode allowed surgeons to have immediate measurements of blood oxygen during surgery, which allowed for open heart surgeries. Dr. Clark not only developed the Clark Electrode, he helped to develop the glucose monitor, which is still critical for many diabetic patients to monitor their care. He also helped to develop the first heart-lung machine helped pave the way for one of the first intensive care units in the world3.

While Dr. Clark was more concerned with measuring oxygen saturation in blood to improve direct patient care, he didn’t realize that he would also greatly advance the field of metabolism by allowing for accurate measurements of mitochondrial function. I personally owe Dr. Clark a debt of gratitude because I wouldn’t be where I am today without his pioneering inventions.

 

References:

  1. https://www.physiology.org/doi/pdf/10.1152/jappl.1953.6.3.189
  2. https://en.wikipedia.org/wiki/Leland_Clark#/media/File:Dr._Leland_C._Clark_Jr_2005.jpg
  3. https://www.ysi.com/about/history

 

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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#AHA19: Why Choose Heart Failure?

“Skate to where the puck is going, not where it has been.” -Wayne Gretzky, Hall of Fame Hockey Player

I heard this quote a few times at #AHA19, most relevantly during a special interest “breakout” session for Advanced Heart Failure & Transplant Cardiology held in the AHA Early Career / FIT Lounge. In reflecting on the hot topics of the meeting, as well as the landmark clinical trials that have been published over the course of my training, I couldn’t help but agree with the following notion discussed in the breakout session:

Heart Failure is where the puck is going.

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Dr. Tariq Ahmad, Dr. Eric Adler, and Dr. Sophia Airhart serving as expert faculty panelists for the Advanced Heart Failure & Transplant Cardiology breakout session in the AHA Early Career / FIT Lounge at #AHA19.

As a current Advanced Heart Failure fellow, I am clearly biased here. But after the field experienced a decade-long drought absent of new effective therapies to improve the outcomes of patients with heart failure, the landscape changed in 2014 with the publication of the PARADIGM-HF trial and its effect of adding angiotensin receptor-neprilysin inhibitor (ARNI) therapy to the armamentarium of cardiologists treating patients with heart failure with reduced ejection fraction (HFrEF).

Fortunately, since PARADIGM-HF, the momentum has continued to build. The addition of effective new therapies for patients with heart failure has not stopped with ARNI. In 2015, with the EMPA-REG OUTCOME trial, we began to see the signal for improved heart failure outcomes (reduced heart failure hospitalizations), with the use of a sodium glucose-cotransporter 2 inhibitor (SGLT2i) in patients with diabetes, generating excitement for the potential for SGLT2i therapy in heart failure. In 2018, we learned of our first effective treatment for transthyretin amyloid cardiomyopathy, which is now FDA-approved and quickly making its way to our patients.

Presentations at #AHA19 kept this wheel turning, as there were key studies presented that continue to shape the new frontier of therapies for heart failure.

  • DAPA-HF: The DAPA-HF trial was the first to study the efficacy of SGLT2i as a heart failure therapy, even in patients without diabetes. While initial results were presented at the European Society of Cardiology (ESC) Congress in September 2019, further insights from the DAPA-HF trial were presented at #AHA19, demonstrating that the significant effects of the SGLT2i, dapagliflozin, on reducing the risk of death and improving heart failure outcomes in HFrEF spanned across the spectrum of ages studied, demonstrating efficacy even in the elderly. Further, dapagliflozin improved the health status in patients with HFrEF, based on the Kansas City Cardiomyopathy Questionnaire.
  • PARADIGM-HF + PARAGON-HF: The results of the PARAGON-HF trial, presented earlier this year, did not show significant added benefit of sacubitril/valsartan therapy in reducing adverse events in patients with heart failure with preserved ejection fraction (HFpEF) compared to valsartan therapy alone. However, a pooled analysis of the PARADIGM-HF & PARAGON-HF trials was presented at #AHA19 by Dr. Muthu Vaduganathan from Brigham & Women’s Hospital. This analysis suggested that the therapeutic effect of sacubitril/valsartan may extend into the heart failure with mid-range ejection fraction (HFmrEF; LVEF 40-49%) range. Interestingly, there appears to also be differential response between men and women to sacubitril/valsartan. The HFmrEF category has been garnering more interest lately, and this study points to a potential benefit of ARNi therapy in this group.
  • VICTORIA: While not presented at #AHA19, the announcement of positive results for the VICTORIA trial was made shortly after the conclusion of the conference. The VICTORIA trial studied the soluble guanylate cyclase inhibitor, vericiguat, in patients with HFrEF, and per the press release, “reduced the risk of the composite endpoint of heart failure hospitalization or cardiovascular death.” This class of medications is most well-known for riociguat’s use in chronic thromboembolic pulmonary hypertension, but, depending on the results of VICTORIA, which will be presented in 2020, it may constitute yet another class of effective medications in the heart failure toolkit.

With new, effective medical therapies continuing to emerge for patients with heart failure, the field is making progress at chipping away at the high mortality rates that still plague our patients with heart failure. With the impending approval of SGLT2i for patients with HFrEF, we are now entering an era of “quadruple therapy” for HFrEF, with significant efficacy if adequately implemented.

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Combine these exciting developments with the concurrent advances in structural therapies (i.e., percutaneous valve repair/replacement) and eventual development of a fully implantable left ventricular assist device (LVAD), I believe that heart failure is a cardiology subspecialty on the rise and that undifferentiated trainees should do one simple thing: Skate to where the puck is going.

 

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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On Mentorship, Leadership, Volunteerism: An Early Career Recap

Throughout my career, I’ve been coached that mentorship is the key to success. I found this to be true throughout my doctoral education, during my stint as a research consultant in industry, as a research fellow in a primarily clinical fellowship, and, now, as junior faculty. I won’t say that I’ve mastered mentorship (or being mentored), but I have been fortunate to benefit from the efforts of some of the best. Here are a few notes that I’ve found helpful in seeking meaningful connections at AHA Scientific Sessions 2019 and beyond:

1. It takes a village to raise a child (and an academic career). Similar to the diversity you would find among village members, I like to use a team-based approach to mentorship. There are different types of mentors with different functions. I’ve found that my mentors fit into at least one of three categories—having similar training and/or experience, interests, or expertise. Some fulfill 2 categories, but very rarely have my mentors matched on all three domains. I find myself as the unifying point in the center.

For example, some of my mentors have earned PhDs. They offer important advice on a career path in academia that includes teaching responsibility rather than clinical load. Other mentors are physician-scientists with shared interests in health equity and or cardiovascular disparities. Still, others may have mastered methods in an entirely different field that I hope to apply to my own. All three make a contribution to my development whether it be learning implementation science or how to manage a clinical trial or balancing the duties of an academician or just being a good person.

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2. Take your seat at the (unknown) table. Sometimes, you find the best mentors in unintended spaces. At the AHA Scientific Sessions, I had the opportunity to attend the “Lunch with Legends” session for early career scientists and trainees to interact with seasoned scientists. In the hustle of running from one end of the enormous Philadelphia Convention Center to the other, I arrived late to find that the list of legends with their bios had been removed. I was going to have to gamble. So, I selected a table where an older gentleman with a friendly face sat with a captivated audience of 3 trainees, who turned out to be one of the leading cardiologists in hypertension among African Americans. (I study hypertension in African Americans!) It seemed serendipitous that I’d landed with a senior scientist with shared interest and expertise from which I could glean.

I’ve learned that more often than not seemingly by-chance opportunities are often the most fruitful. Because I’m interested in personal narratives (see blog), I always ask senior scientists how they found their niche. Most often than not the answer is that they were moving about their work and they were offered the challenge to do something that they’d not yet done—to consider a topic that they hadn’t considered or to work with a person with a different perspective or expertise. There’s apparent synergy in the mild friction at the interface of differences that may carve out entirely new spaces.

3. Think globally, act locally. Most would recognize this quote as an environmental call to action. I would argue that it also applies to approaching volunteerism in our personal careers. In the Go Red Women in Science and Medicine Lounge, Drs. Stacy Rosen and Michelle Albert spoke about Volunteerism to Advance Your Career. One of the main take-home messages from this session (as interpreted by me) was that lending your services and expertise at local AHA chapters may build opportunities to work in larger capacities on bigger stages. As young professionals, volunteering in local efforts builds our capacity to lead in broader contexts.

Being an effective leader—of teams, of labs, of thought—is a required complement to scientific expertise to succeed in academic medicine. As it relates to points 1 and 2 above, we may also find that some of our most impactful mentors aren’t scientists at all.

 

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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3CPR Shark Tank Competition at AHA19: “Fish are Friends, Not Food!”

Some of the highlights of AHA19 for me include seeing the support that the AHA and many established cardiovascular leaders who are part of the AHA give to early career investigators and to see some of the amazing work completed by trainees. Specifically in the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation (3CPR), there were many opportunities for trainees to showcase their work at AHA19 including at poster sessions, moderated poster sessions, the Cournand and Comroe Early Career Investigator Award Competition, Kenneth D. Bloch Memorial Lecture in Vascular Biology, and one of my favorite sessions that I watched this year, the 3CPR Shark Tank Competition.

To follow my previous blog post on mentorship, this post will discuss the 3CPR Shark Tank Competition, an opportunity for trainees to receive mentorship from an established leader in cardiovascular medicine at another institution.

shark tankThe TV show, Shark Tank, is a reality TV show where entrepreneurs pitch business ideas to a panel of investors known as “sharks” who then decide whether to invest in the entrepreneurs’ businesses. Similarly, in the 3CPR Shark Tank Competition, early career candidates present their proposed research project to the “sharks” who are leaders in cardiovascular medicine. Winners receive mentorship from a mentor that is not at their home institution. Specifically, the winners receive a sponsored visit to the mentor’s institution to present research or attendance at a future conference with the mentor, the mentor will review the mentee’s future grant aims page, and there are three phone calls over a year between the mentor and mentee to review data and progress towards establishing the mentee’s research program. The AHA and “sharks” contribute money to defer the costs of travel for the mentee. The goals of the Shark Tank Competition are to highlight some of the most promising junior investigators and leaders in 3CPR, promote new ways of mentorship, and show early career members what some of the important issues when presenting research ideas are from a senior perspective.

Dr. Kimberly Dunham-Snary, a postdoctoral fellow in Dr. Stephen Archer’s lab at Queen’s University and winner of the 2018 Shark Tank Competition spoke very highly on the mentoring that she received after winning the 3CPR Shark Tank Competition: “Dr. Rabinovitch organized a mock faculty interview for my visit to Stanford and [I] met with numerous faculty one-on-one. I received advice about everything from chalk talk to grantsmanship to mentoring strategies. This definitely helped me prepare for my current faculty interviews. Thanks so much to Dr. Rabinovitch and to 3CPR for proving me with this training opportunity!”

Selected candidates to present in the 3CPR Shark Tank Competition had a top scoring abstract submitted to AHA Scientific Sessions or the Resuscitation Sciences Symposium (ReSS) and must be an early career investigator who is at the end of his/her postdoctoral fellowship and is planning on transitioning towards independence. Ideal candidates are looking to submit a K or AHA Career Development grant application in the next year. Each candidate has four minutes to present their proposed research program/project and the candidates can only have a single slide to support their presentation. The “sharks” then have seven minutes to clarify, question, critique, and vie for the affections of the candidates. Winners are selected by the “sharks” and audience scoring, each accounting for 50% of the final score.

This year was the second annual 3CPR Shark Tank Competition. The competition began with the “sharks” reciting the Shark Pledge in the movie, Finding Nemo (“I am a nice shark, not a mindless eating machine. […] Fish are friends, not food!”)1. This year’s “sharks” were Dr. Mark Gladwin from University of Pittsburgh; Dr. Jane Leopold from Brigham and Women’s Hospital; Dr. Robert Neumar from University of Michigan; Dr. Werner Seeger at the Max-Planck Institute for Heart and Lung Research and Universities of Giessen and Marburg in Germany; Dr. Marc Semigran, chief medical officer of MyoKardia; and Dr. Terry Vanden Hoek at the University of Illinois in Chicago. Winners of this year’s Shark Tank Competition were Dr. Alexis Steinberg, Neuro-Critical Care Fellow at the University of Pittsburg; Dr. Taijya Satoh, postdoctoral fellowship in Dr. Gladwin’s laboratory at University of Pittsburg; and Dr. Rajat Kalra, Advanced Imaging Fellow at the University of Minnesota.

Not only is the 3CPR Shark Tank Competition a great opportunity for trainees who are in 3CPR to participate in, it was very entertaining to watch. I think that since the competition was at night around dinner time, as the evening progressed, the “sharks” may have gotten a little more irritable and had to be reminded that minnows are friends. I encourage FITs in 3CPR to consider participating in the 3CPR Shark Tank Competition in the future and for all trainees in 3CPR and any other council to consider watching this entertaining competition in the future!

 

References:

  1. Finding Nemo. Directed by Andrew Stanton and Lee Unkrich, Walt Disney Pictures, 30 May 2003.

 

Acknowledgments:

Thank you to Dr. Kurt Prins, one of the organizers of the 3CPR Shark Tank Competition, for providing me with information about the Shark Tank Competition and to Dr. Kimberly Dunham-Snary for allowing me to share her feedback on her experience with the Shark Tank Competition.

 

 

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.