Early Career Blogger

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

• 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.

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.

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 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 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 world^3.

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.

“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.

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.

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.

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.

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.

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.

The 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.

Created in 2006, Twitter became a new form of social media. I joined, but wasn’t very active. If someone were to have told me that tweeting would be a way for me to stay up to date in my field of pediatric cardiology, to network with people professionally and to share in experience with a community of physicians, I probably would have laughed.

Fast forward to November of 2019 and I am sitting in my first conference as an AHA Early Career Blogger, busy “live tweeting” updates, “hash-tagging” and connecting, hoping I could help spread the work and engage the audience that couldn’t travel or make their way to the sessions. I also found myself searching the #AHA19 hashtag for information on other things going on at the conference or programs I may have missed. This allowed me to learn from the many different coinciding lectures without being in several places at once.

So why should you get on Twitter if you aren’t already?

1. Twitter can be a great opportunity for you to learn from conferences you cannot attend in person, or parts of conferences you may miss. One of the best ways to get involved in this is following the society’s twitter page, such as @AHAmeetings and @AHAscience, this is often the source of the conference “hashtag” with updates on when, who and how to follow and when other conferences are coming. Your “twitter community” can also be a good source for these.
2. Twitter is a great way to get to know people and science in your field. Finding your twitter community can take some searching, but it’s pretty easy. For example, there is #cardiotwitter, #medtwitter, #tweetiatricians, and more! Just do a simple search with key words and start looking for people, topics and hashtags to follow.
3. Twitter is a great opportunity to discuss challenging or interesting cases (with patient permission of course) with a world of minds at your fingertips; providing an area to connect with healthcare providers at other institutions to share ideas and collaborate. You can use your community’s hashtag to help engage them and so it’s easily searchable. Twitter also allows you to create polls to ask questions.
4. Twitter can provide a community of people who understand the stress, demands and struggles we deal with as physicians. Communities such as #SoMe and #womeninmedicine often post about what it’s like to be a physician and provide helpful “tweetorials” or online discussion on topics from medicine to wellness.
5. Twitter provides a way to connect with the community, to advocate and to explore; there are more than just physicians on twitter and a world of opportunities to explore. Plus, some people on social media can be quite entertaining. Make sure to spice up your twitter with other things that interest you outside of medicine likes sports, news and entertainment!

Is there a downside to Twitter? As with any technology and social media, it can be addicting; if you post an opinion you may be met with resistance or a crowd of people who disagree; and some may simply find Twitter isn’t for them. But overall, the community, the learning and the networking opportunities to me, outweigh the downsides, and like all things, use in moderation is key.

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.

The past few years have witnessed the emergence of many technological advances that hold promises for potentially revolutionizing the way we are treating patients with cardiac arrhythmias. Between innovative technologies for cardiac pacemakers and defibrillators, breakthroughs in ablation of atrial and ventricular arrhythmias, and boundless progress in remote monitoring of cardiac rhythm, the field of clinical electrophysiology (EP) is undergoing an exhilarating conceptual transformation.

The American Heart Association (AHA) 2019 Scientific Sessions that took place in Philadelphia last month, have dedicated an excellent session to highlight and summarize these recent EP advances. A session that brought together prominent EP leaders and innovators discussing the present and the future of the field, which, to an aspiring electrophysiologist like myself, has been one of the most inspiring sessions of the conference. The title was catchy: “Hottest New EP Advances and Connections with the Experts”, and despite being an evening session, the large conference room was packed with EP enthusiasts at different stages of their careers. It was around an hour and a half of tour-de-force presentations by an outstanding group of speakers. The amount of valuable information presented is more than what can be captured in a short essay, yet, I will highlight the most promising technologies in my humble opinion.

I will start with cardiac implantable electronic devices (CIEDs), where several technological and conceptual breakthroughs have recently made their way to clinical practice, and many more are expected to do so in the near future. The 3 most exciting frontiers are:

• The leadless intra-cardiac pacemaker system, which was approved by the FDA in April 2016. The device is the size of a large vitamin capsule, implanted percutaneously. This new technology allows cardiac pacing in the absence of intravenous leads and subcutaneous pulse generators, which not only is more convenient for patients, but also avoids lead and pocket-related complications.¹ The current commercially-available system is only capable of single-chamber sensing and pacing, however, the results of the MARVEL 2 study,² demonstrating the safety and efficacy of an accelerometer-based VDD pacing algorithm to maintain AV synchrony with the leadless pacemaker system, were just released at AHA19. Newer technologies that are expected in the next few years include atrial leadless pacemaker and leadless multicomponent systems, for instance using endocardial left ventricular electrodes as part of cardiac resynchronization therapy.
• The new subcutaneous implantable cardioverter- defibrillator (ICD) technologies. The original subcutaneous ICD was approved by the FDA in September 2012 and has been widely used in clinical practice.³ This technology provides a defibrillator option for patients with challenging anatomy for conventional intravascular ICD implantation, and with no indication for pacing. Newer promising technologies in the field of subcutaneous ICDs that are not commercially available yet include string subcutaneous ICD – with no can, hence no need for a surgical pocket – and extravascular ICD which is capable of pacing the myocardium in addition to delivering ICD shocks, while being completely extravascular. Combining subcutaneous ICDs with leadless pacemaker systems is another exciting area of future research.
• His bundle pacing and left bundle branch pacing, which are new physiological alternative to right ventricular pacing, and potentially to bi-ventricular pacing in patients with proximal left bundle branch block, through engaging the normal conductive His-Purkinje system and, therefore, avoiding the long term deleterious effects of ventricular dyssynchrony. As opposed to the above-mentioned technological breakthroughs, this is more of a slow ongoing learning process, which has been around since the early 2000’s, initially performed with the already-available standard pacing leads with reshaped or deflectable stylets, limited by technical difficulties. However, the more recent use of a solid core lead in conjunction with specialized sheaths has sparked new interests in this pacing technique, which is being increasingly adopted in clinical practice and eventually made its way to the most recent pacing guidelines.⁴ The future likely holds the development of more specialized equipment designed specifically to facilitate these pacing approaches.

Switching gears to the field of cardiac ablation, the other major pillar of EP interventions. The most promising, and potentially revolutionary advances in this area are:

• Non-invasive radio-ablation of ventricular tachyarrhythmias (VT). VT ablation is known to be associated with increased risk of procedural complications given the sick phenotype that these patients commonly present with, in addition to the length of the procedure, catheter manipulations inside the left ventricle and the need for induction of VT, which makes the procedure more challenging and more risky compared to other forms of cardiac ablation. The use of stereotactic body radiation therapy (SBRT) to ablate VT in a radiology suite, aided by non-invasive cardiac mapping using electrocardiographic imaging, is undoubtedly one of the most exciting recent breakthroughs in the field of EP. The use of radiotherapy not only mitigates the procedural risks of catheter-based ablation, but also allows reaching myocardial foci that are not accessible by conventional endocardial or epicardial approaches. Although the available data are merely preliminary,⁵ and more research is needed prior to the widespread use of this procedure in treating patients with VT, the concept is very promising and the potential implications are remarkable. The potential use of SBRT in treating other arrhythmias such as atrial fibrillation (AF) is also under investigation.
• Pulsed Field Ablation (PFA) for pulmonary vein isolation (PVI). Indiscriminate tissue destruction with potential damage to surrounding structures such as the esophagus and the phrenic nerve has been the major barrier to delivering reliable ablation lesions that ensure durable PVI in AF patients. This new ablation technology uses a process called electroporation, for which cardiac myocytes are most sensitive, potentially allowing selective cardiac ablation. The results of the IMPULSE and PEFCAT studies were recently published, and demonstrated an impressive 100% PVI durability at 3 months with this technique, with an average skin-to-skin procedure time of only 92 minutes. Importantly, there were no evidence of esophageal or phrenic nerve damage, despite the lack of use of an esophageal protection strategy.⁶ The ability to safely deliver deep ablation lesions in the atrium without damaging the surrounding extra-cardiac tissue can potentially transform the success rates of catheter ablation for AF and may expand the use of this technology to other forms of arrhythmia ablations.

Listening to world-renowned EP experts enthusiastically walking the audience through these various breakthroughs and painting a futuristic picture of how the world of EP can look like in the near future, left me thinking about how lucky I am to be starting my EP training in this exciting era of technological revolution. Witnessing the transformation of a cardiac subspecialty is exciting, but the possibility of being part of this transformation is mind-blowing!

References:

1. Reynolds D, Duray GZ, Omar R et al. A Leadless Intracardiac Transcatheter Pacing System. N Engl J Med. 2016;374:533-41
2. Chinitz LA, Khelae AK, Garweg C et al. Atrial Synchronous Pacing Using a Leadless Ventricular Pacemaker: Primary Results From the MARVEL 2 Study. Presented at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019
3. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P110042. Accessed November 30, 2019.
4. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay. Circulation. 2019;140:e382–e482
5. Robinson CG, Samson PP, Moore KMS et al. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation. 2019;139:313–321.
6. Reddy VY, Neuzil P, Koruth JS et al. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol. 2019;74:315-326.

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.

AHA19 was a tremendous meeting for many reasons – extraordinary science, inspirational attendees, performances from the cast of Hamilton, and all in my current home of Philadelphia! Sessions 2019 was also unique for its deliberate approach to the inclusion of women in cardiovascular and neurovascular medicine. I was impressed by the breadth and depth of programming related to women and the open discussions of issues facing women in medicine. If you missed this thread of Sessions 2019, here are some highlights:

1) President Harrington’s Presidential Address: In AHA President Robert Harrington’s Presidential Address, he noted that over the last 7 years as a department and health system leader, he has become increasingly concerned with the lack of diversity in cardiovascular medicine. He also proclaimed that the male : female ratio in cardiovascular medicine is “out of whack” – a sentiment that drew rounds of applause from the audience.  He shared some startling demographic data regarding the cardiovascular workforce, including the fact that 12 states have fewer than 10 practicing women cardiologists. The AHA’s newly formed Go Red for Women in Science and Medicine Committee is tackling implicit and explicit gender biases in all of its science activities, including grant submission and peer review processes. Dr. Harrington closed this part of his speech by emphasizing the imperative upon men in power to recognize and address these disparities in cardiovascular medicine. Despite lasting less than 5 minutes, this segment of his Address was captivating, and his impassioned case for diversity and inclusion drew multiple ovations from the audience.

2) No Manels: Dr. Harrington also announced that at AHA19 there were no all-male speaking panels, or “manels”! Earlier this year, the Director of the National Institutes of Health, Dr. Francis Collins, announced that he would no longer participate in manels or other events in which “inclusiveness is not evident in the agenda.” In his statement, he challenged other scientific leaders to do the same. When Dr. Harrington announced that he, Dr. Donald Lloyd-Jones, Dr. Manesh Patel, and AHA leadership had eliminated the manel at AHA19, I felt proud to be a part of an organization that prioritized this commitment to inclusivity in the scientific program and in a public way. The AHA has now set the standard for gender representation at cardiovascular conferences, and I am looking forward to where we go from here.

3) Women Across the Program: When I searched the word “women” in the AHA19 Sessions App, I found a total of 173 abstracts, oral presentations, luncheons, dinners, and Lounge sessions spanning career development, basic, translational, clinical, implementation, and population science. Not only were women leading at the podiums and panels, but there was an explosion of featured research in women’s cardiovascular health, cardio-obstetrics, sex differences in pathophysiology, diagnostics, therapeutics, and outcomes across the spectrum of cardiovascular disease.  In addition, the Women in Science and Medicine Lounge hosted high-yield career development programming for women throughout the weekend with sessions on mentorship, sponsorship, volunteerism, social media, negotiations, storytelling, mindfulness, and more. In the AHA Fellow in Training (FIT) and Early Career Lounge, we held a fantastic session on self-advocacy as a woman in medicine with insights from Drs. Harriette Van Spall, Biykem Bozkurt, Mary Cushman, and Monika Sanghavi. In his Address, Dr. Harrington also announced a new AHA partnership called Research Goes Red, a technology platform powered by Verily and Project Baseline to engage 1,000,000 women to contribute their health data toward research into heart and brain health, with a focus on millennial women from underrepresented ethnic and racial groups.

In my advocacy work, I have learned that women are usually successful at engaging and empowering other women to support the mission of diversity and inclusion in cardiovascular medicine, but it is often easy for other populations to remain at a distance, divorced from and uninvested in these efforts. In many ways, AHA19 brought this dialogue to the center stage and demonstrated to our trainees and early career members that we are indeed making strides toward an equitable and just future for women in cardiovascular medicine.

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.

The American Heart Association’s Scientific Sessions is one of the biggest conferences in cardiology. It draws students, residents, fellows, affiliate practitioners, attendings, researchers, and so many more. Therefore, attending a conference of this caliber is a big deal! The event is full of intense information. New ideas. New contacts. New solutions. And, new found energy. Most of us are revitalized after any scientific session which I believe is due to a multitude of factors including: meeting experts in our field, seeing new clinical trials, attending small group sessions for a more intimate experience, and reconnecting with friends and colleagues. Eventually, the conference comes to an end and we go our separate ways. Seems as we get closer to home, the exhaustion from the trip and the ensuing clinical responsibilities become more of a reality. This massive surge of energy is quickly plummeting. As an early career FIT, we have several responsibilities that can quickly take away from the momentum we have built during the sessions so how do we continue to sustain it?

• Write: As soon as I get home or even every night at the conference, I jot down my thoughts. This helps me prioritize what is important for me to focus on once the conference is over.
• Speak to your program leadership: When I came back from AHA 19, I had an inform discussion with my program leadership on the entire conference and what I learned. Specifically, I used this time to discuss how I can accomplish the goals I have set forward. The leadership is well aware of the program strengths/weaknesses but more importantly, others who can help mentor me in achieving my goals.
• Debrief with your co-fellows: After the sessions, the entire fellowship class can get together to discuss ideas for quality improvement, collaborate research, or changes they would like to implement in the fellowship. This is a great way for junior fellows to start getting involved in existing projects if they feel starting one of their own will be too daunting.
• Reach out: Hopefully you were able to network while you attended the sessions. I always reach out to the people I met asking for advice or if they are looking to collaborate on projects. I’ll also reach out if I have a question regarding how to care for a complex patient – after all, the scientific sessions are a fantastic time to meet providers who are considered experts in their fields. This continues to foster a professional relationship for years to come. Conferences are a great time to see what is “hot” in cardiology and meet the individuals that are leading the charge. Take advantage of this unique opportunity to cultivate your career.
• Sign up For Another AHA Conference: Remembering how good I feel after a conference helps me stay motivated. Whenever I’m dragging my feet, I revisit the ideas I wrote down in the first point to remind myself how much I learned, wanted to accomplish, and the new network I created. Having another conference to attend helps me stay motivated and not lose steam on projects.

Hopefully, these five easy tips will help keep the momentum going strong long after the conference is over to continue to be successful.

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.