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The Clock is Ticking: Door-to-Needle Time in Acute Ischemic Stroke

Lay of the Land

In 2008, after years of being the third-leading cause of death in the United States, stroke dropped to fourth. In part, this reflected the results of a commitment made by the American Heart Association/American Stroke Association (AHA/ASA) more than a decade prior to reduce stroke, coronary heart disease, and cardiovascular risk by 25% by the year 2010 (a goal met a year early in 2009). The reason for the success, although multifactorial, can largely be attributed to improved prevention and improved care within the first hours of acute strokes.1 As early as 2000, the benefits of time-dependent administration of intravenous tissue plasminogen activator (tPA) in patients with acute ischemic stroke were well supported (Figure 1).2

Figure 1. Graph of model estimating OR for favorable outcome at 3 months in recombinant tissue-type plasminogen activator (rt-PA) treated patients compared to placebo treated patients by time from stroke onset to treatment (onset-to-treatment time [OTT]) with 95% confidence intervals, adjusting for the baseline NIH Stroke Scale. OR > 1 indicates greater odds that rt-PA treated patients will have a favorable outcome at 3 months compared to the placebo treated patients. Range of OTT was 58 to 180 minutes with mean (μ) of 119.7 minutes.2

Guidelines began recommending a door-to-needle time for tPA administration of 60 minutes or less, however, studies found that less than 30% of US patients were treated within this time window. The Target: Stroke initiative was launched in 2010 to assist hospitals in providing timely tPA. As a result, the proportion of tPA administered within 60 minutes increased from 26.5% during the preintervention period to 41.3% after implementation. Despite national initiatives, shorter door-to-needle times have not been as quickly adopted as door-to-balloon times for percutaneous coronary intervention in acute coronary syndromes (Figure 2).4 Part of the problem is a lack of robust mortality outcomes data to support trends observed in the (only) two randomized trials conducted to assess long term outcomes with tPA in acute ischemic stroke; neither of which was powered to probe for mortality effects.

Figure 2. Trend in percentage of patients with door-to-balloon (D2B) time <90 minutes over 6 years.4

This brings us to the study published earlier this week in JAMA Man S et al. (corresponding author Fonarow GC) titled “Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke.” This nationwide study of US patients treated with intravenous tPA for acute ischemic stroke demonstrated that shorter door-to-needle times were significantly associated with better long-term outcomes, including lower 1-year all-cause mortality, 1-year all-cause readmission, and the composite of all-cause mortality or readmission at 1 year.5

Study Design

This US cohort included Medicare beneficiaries aged 65 years or older who were treated with intravenous tPA for acute ischemic stroke at Get With The Guidelines (GWTG)–Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017. Patient clinical data were obtained from the GWTG-Stroke database. Study entry criteria required patients to (1) have been aged 65 years or older; (2) have a discharge diagnosis of acute ischemic stroke; (3) have been treated with intravenous tPA within 4.5 hours of the time they were last known to be well; (4) have had a documented door-to-needle time; (5) not have been treated with a concomitant therapy with intra-arterial reperfusion techniques; (6) have had the admission be the first for stroke during the study period; and (7) not have been transferred to another acute care hospital, left against medical advice, or without a documented site of discharge disposition.5 Overall, 61426 participants met the inclusion criteria for the study.

The prespecified primary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, and the composite of all-cause mortality or readmission at 1 year. One-year cardiovascular readmission was a prespecified secondary outcome and was defined as a readmission with a primary discharge diagnosis of hypertension, coronary artery disease, myocardial infarction, heart failure, abdominal or aortic aneurysm, valvular disease, and cardiac arrhythmia. Recurrent stroke readmission, a post hoc secondary outcome, was defined as a readmission for transient ischemic attack, ischemic and hemorrhagic stroke, carotid endarterectomy or stenting, but not for direct complications of index stroke.5

Door-to-needle time was first analyzed using the prespecified times of within 45 minutes and within 60 minutes versus longer than those targets, in line with prior studies on this topic. The authors also ingeniously also evaluated time as a continuous variable, as a categorical variable in 15-minute increments using within 30 minutes as the reference group, and in 45-minute and 60-minute increments. Cox proportional hazards models were used to examine the associations of door-to-needle timeliness and each 1-year outcome with robust variance estimation to ac- count for the clustering of patients within hospitals.5 On hours were defined as 7:00 AM to 6:00 PM on any weekday. Off hours were defined as any other time, including evenings, nights, weekends, and national holidays. The authors did this because prior studies using this prespecified time cutoff have shown that presenting during off hours was associated with inferior quality of care, inferior intravenous thrombolytic treatment, and in-hospital mortality.5

Results

Among the 61426 Medicare beneficiaries treated with intravenous tPA within 4.5 hours of the time they were last known to be well at the 1651 GWTG-Stroke participating hospitals, the median age was 80 years, 43.5% were male, 82.0% were non-Hispanic white, 8.7% were non-Hispanic black, 4.0% were Hispanic, and 5.3% were of other race/ethnicity. More patients that arrived during off hours were treated within longer door-to-needle times (40.7% for ≤30 minutes, 45.6% for 31-45 minutes, 50.6% for 46-60 minutes, 53.5% for 61-75 minutes, and 56.3% for >75 minutes; P < .001). Despite having longer onset-to-arrival times, some patients had shorter onset-to-needle and door-to-needle times.5

Most patients were treated at teaching hospitals (77.7%) and primary stroke centers (73.2%); 3% were treated at rural hospitals. More patients who were treated at teaching hospitals, but not at primary stroke centers, were treated within shorter door-to-needle times. The median door-to-needle time was 65 minutes, with 5.6% of patients treated with tPA within 30 minutes of hospital arrival, 20.8% within 45 minutes, and 44.1% within 60 minutes.5

Patients who received tPA after 45 minutes of hospital arrival had worse long-term outcomes than those treated within 45 minutes of hospital arrival, including significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted hazard ratio [HR], 1.13 [95% CI, 1.09- 1.18]), higher all-cause readmission (40.8% vs 38.4%; ad- justed HR, 1.08 [95% CI, 1.05-1.12]), higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]), and higher cardiovascular readmission (secondary outcome) (19.8% vs 18.4%; adjusted HR, 1.05 [95% CI, 1.00- 1.10]), but not significantly higher recurrent stroke readmission (a post hoc secondary outcome) (9.3% vs 8.8%; adjusted HR, 1.05 [95% CI, 0.98-1.12]).

Patients who received tPA after 60 minutes of hospital arrival vs within 60 minutes of hospital arrival had significantly higher adjusted all-cause mortality (35.8% vs 32.1%, respectively; adjusted HR, 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]), and higher cardiovascular readmission (secondary outcome) (20.2% vs 18.6%; adjusted HR, 1.06 [95% CI, 1.01-1.10]), but not significantly higher recurrent stroke readmission (a post hoc secondary outcome) (9.3% vs 8.9%; adjusted HR, 1.03 [95% CI, 0.97-1.09]).

The absolute differences in outcomes increased with longer door-to-needle times. The cumulative incidence curves showed that approximately 42% of the deaths or readmissions occurred within 30 days.

Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05] for door-to-needle time within 90 minutes of arrival. However, this association did not persist beyond 90 minutes of hospital arrival. Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause readmission (adjusted HR, 1.02 [95% CI, 1.01- 1.03]) and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]). Every 15-minute increase in door-to-needle times after 60 minutes of hospital arrival was significantly associated with higher cardiovascular readmission (secondary outcome) (adjusted HR, 1.02 [95% CI, 1.01- 1.04]) and higher stroke readmission (a post hoc secondary out- come) (adjusted HR, 1.02 [95% CI, 1.00-1.04]); however, these associations were not statistically significant for the door-to-needle times within 60 minutes of hospital arrival.

My Take

I would first like to commend the authors on this undertaking. The fact that early door-to-balloon time is still questionable seems contrary to our understanding of ischemic events and time to cell necrosis. This high-quality study further supports the notion that “time is muscle,” as seen in other ischemic events such as acute myocardial infarction and acute limb ischemia. However, the limitations of the study affects its generalizability and application to real world scenarios. The patients in this study are all over the age of 65, largely non-Hispanic whites, all with recorded times of last seen normal and mostly treated in academic centers with stroke units. Nonetheless, the authors have certainly progressed the field of stroke treatment, if even incrementally, in the right direction.

References:

  1. Jauch EC, Saver  JL, Adams  HP  Jr,  et al; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology.  Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.  Stroke. 2013;44(3):870-947.
  2. Marler JR, Tilley  BC, Lu  M,  et al.  Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study.  Neurology. 2000;55(11):1649-1655.
  3. Fonarow GC, Zhao X, Smith EE, et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA. 2014;311(16):1632- 1640. doi:10.1001/jama.2014.3203
  4. Krumholz HM, et al. Improvements in door-to-balloon time in the United States, 2005-2010. Circulation 2011;124:1038-45.
  5. Man S, Xian Y, Holmes DN, et al. Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke. JAMA. 2020;323(21):1-15. doi:10.1001/jama.2020.5697

“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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Should you keep politics out of your career?

Advocacy is a core function of many health professions, including nursing and medicine. So why are we socialized not to engage with politically touchy subjects at work?

Funding for much of our work in science, medicine, and education comes from the government. Sometimes it comes from corporations that make pharmaceuticals or devices. Even in democracies like the U.S., legally protected free speech does not prevent organizations from restricting their employee’s participation in political activities or certain kinds of speech while working.

The current global public health crisis is igniting fierce debates around hot-button issues of workforce safety, inequality, prejudice, disparities, and personal freedoms. As the world changes rapidly, I am hearing lots of early-career folks wondering how to balance the call to engagement on divisive topics with the need for career stability. My profession, nursing, has a long history of activism and political engagement. I also work for a large university, where political engagement can rock the boat and raise eyebrows. This is a precarious position.

Here’s the rub: public health issues are inherently political. Think of political advocacy around tobacco and vaping, and food. These are everyday public health concerns and they are steeped in politics, yet they rarely result in career-ending political feuds; this kind of politics is generally tolerated in academic institutions. However, as we are now seeing, the relationship between politics and public health is stronger with rare and catastrophic events like the COVID-19 pandemic. Those of us in science and health professions are facing the ramifications of political decisions daily, such as access to PPE supplies, access to ventilators and medications, guidance to the public about masks and distancing, and travel restrictions. We feel this impact acutely, and many of us feel compelled to voice our opinions.

Yet, we may find ourselves at risk if we speak up about an issue with political implications, either at work or in outside public forums. Voicing dissent to institutional policy, governmental policy, or anything in between can be professionally and personally damaging. In the U.S., hospitals have been ordering staff not to speak to the media and terminating those who do not comply. This behavior can have a chilling effect on others’ willingness to voice concerns about safety. As a result of these gag orders, high-level decision-making is often missing key voices and information. The case of Dr. Li Wenliang, the Chinese physician who sounded early warnings of the dangers of the novel coronavirus, was reprimanded by the Chinese government, and later died of the disease, is a tragic example of just how the stakes are. Navigating the boundaries of political and scientific speech in life-or-death situations is not something we learned in graduate school.

The relationships among scientific data, lived experience, and government messaging are complicated, but that doesn’t mean they are untouchable in a professional context. Medical journals do not universally shy away from political perspectives. The Lancet, for example, recently  published an opinion piece pulling no punches in its assessment of American political leadership: Michael Marmot writes, “Apart from the mendacity, incompetence, narcissism, and disdain for expertise of the man at the top, there may be strong messages about the nature of US society and the response to the pandemic.” Not all professionals and academics are willing to voice such forceful political opinions, but this example shows that even strongly worded opinions can be embraced.

Can mixing politics and work hurt your career? Definitely. Is it possible to practice your profession apolitically? Maybe. Is that something you want to do? You have to decide.

“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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Scientific Sessions during the pandemic

I didn’t know what to expect when I logged in to the American Heart Association’s Quality of Care and Outcomes Research Scientific Sessions earlier this month but having attended I’m definitely a fan of this new virtual format. As a trainee, the largest barriers to attending conferences are usually finding the funding and arranging the time off from work. Not having to worry about missing work on Friday and the cost of a roundtrip flight and hotel for the weekend was a huge positive.

In the couple of weeks since the conference, it’s also been great having access to sessions I missed. With so much going on during the live scientific session, it’s easy to miss a lot of really interesting new research being presented. Being able to go back a couple of weeks later and look through the content has made it much more digestible and eased any fear of missing out I had.

It did take me a little bit to get comfortable navigating the HeartHub (https://www.hearthubs.org/qcor), but then again I usually get turned around at in-person conferences too. Once I was in virtual sessions, I was surprised by how interactive the chats were and how relaxed they felt. Not sure why it felt less formal than an in-person conference but “attending” while having a coffee in my living room, rather than wearing a suit in a conference room sure didn’t add any stress.

Looking forward to #AHA20 online!

“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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What will training look like in the post-pandemic era?

I remember my first week of internship very clearly – I was a part of my first code blue as a physician. Later that week, I had to have a goals of care discussion with a patient who had been in the hospital for 3 weeks (longer than I had been a doctor at that point). These were new experiences that I was eager for, but I was fortunate to have my routine that maintained a sense of normalcy for me, very much like naptime to my toddler. I was diligent in pre-rounding and seeing all my patients before my attending showed up, and would have formed a plan for their care before 8 AM.

Once the COVID-19 pandemic was in full swing here in the US, a lot of these things that were part of my routine as an intern suddenly went to the wayside. At my institution, interns were instructed not to pre-round on patients such as to minimize contact and potential infection transmission. Family meetings could only be conducted via telephone, or in some cases, video conference. Code blues were no longer a mad dash to the patient’s room, but rather, different hospital wards had different teams, such that a provider taking care of COVID+ patients does not go to a code blue for non-COVID patients and vice versa.

Rounding on these revamped inpatient teams has been…interesting to say the least. I can’t tell you the amount of times I or an attending will ask the patient a question about the patient and the response is “I don’t know, I haven’t seen them.” It’s great that interns are more comfortable admitting they don’t know something rather than lie about it, but at the same time, I can’t help but feel a sense of lack of ownership on their behalf.

Everybody will tell you that intern year sucks, and it’s rough, and they would hate to go back and do it again. But many people will also admit that they are impressed with how much they have learned and managed to push themselves beyond their perceived level of comfort during that time frame. I didn’t particularly enjoy coming to the hospital early each day I was on an inpatient service just to see my patients and review their charts, or going to the patient’s room for the umpteenth time in a day, but there have been a number of times where something meaningful was gleaned, and my ability to think critically and manage patients independently grew a little that day.

The thing that bothers me the most about these precautions is the huge change to goals of care discussions and family meetings. The logic behind it – minimizing spread of infection and exposures – makes sense and I agree with it completely. But it’s hard to develop good rapport with an individual only over the phone, and similarly, it’s difficult to comfort another human being digitally. There’s something about the physical presence of another person, the eye contact, and even the slightest gestures, that can help make the worst day of someone’s life a little less painful.

It’s quite fortunate that these protocol changes came more than halfway through the academic year, when interns at least have a handle on what things to look out for and have developed their own sense of alarm from glancing at the chart. I can’t imagine starting intern year where I only physically interact with “my” patients during rounds with my attending, or via telephone, unless there is some kind of emergency.

On the other hand, this is accelerating our embrace of telemedicine on the outpatient side, which is good for both patients and providers in many cases, and from my anecdotal experience, has resulted in a lot fewer “no-shows.” Interns are afforded more sleep, and arguably learning to pay more attention to vital signs changes and lab value changes – or at least they’re getting a better sense of when they should actually get up and go see the patient (sometimes at the urging of their senior 😊). This could simply be an inevitable step in the evolution of medical education that was accelerated by the pandemic, but I can’t say I feel that all these changes should be here to stay.

Whether it was fumbling through morning rounds and trying to formulate a new plan based on overnight events, or developing my emotional intelligence and flexing that empathy muscle, these were formative experiences for me during my intern year that have significantly contributed to my development as a clinician. These could just be the ramblings of a dinosaur, much akin to the older physicians talking about their paper charts, fibrinolytics and 48 hour calls, but I do hope some of these changes can be undone soon, for the sake of our trainees as well as our patients and their families.

“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 COVID-19 Pandemic: A Master Class in Health Inequity

In my course, Social and Economic Determinants of Health Disparities, we spend the semester discussing the complex web of factors rooted in social and economic policies that propagate disparities in health. These include education, employment, housing, broader neighborhood structures and, of course, healthcare. We also contextualize individual and interpersonal health behaviors within those structures. When news of the virus really gained steam in mainstream media, one of my students commented that this was an “inverse disparity”—that predominantly rich, white people who’d vacationed in far-off places were affected. I assured him that as data by race and ethnicity surfaced, we would find minorities bearing the brunt of the burden. Unfortunately, as data began to roll in state-by-state, my prediction was accurate. Further, I knew that this was bigger than who was or wasn’t wearing a mask in public, or of the disproportionate number of minorities with pre-existing conditions that may place them at higher risk. It is about a system that consistently favors the physical, mental, emotional, and financial health of certain sects of the population over others.

When the novel coronavirus came to the US public’s attention just months ago, very few of us expected that our lives would change as much as it has in subsequent months. There were so many uncertainties with this unique virus—its transmission, incubation period, symptoms, and appropriate treatment—that we were left whirling in unpreparedness. US culture, built on the foundational value of individual freedom, found itself at odds with the need to protect a more social interest: stopping the spread.

Our best defensive effort was to stay away from each other, or social distancing—a solution (with all of its benefits) that is fundamentally steeped in privilege. It didn’t account for an invisible, operational background of millions of people who occupy the less educated, often undervalued workforce who, ironically, have come to be regarded as “essential”. There are people who must travel on crowded buses to work elbow-to-elbow in order to feed us, sanitize spaces that we might encounter, and help maintain a semblance of normalcy. While some of those workers may view their efforts as an act of service, there is undoubtedly some life or death decision-making happening. On the one hand, they face the risk of exposure to a potentially deadly virus. On the other hand, they face the equally compelling risk of not being paid if they choose not to show up to work, or if they fall ill. For many, there is really no choice at all: the financial strain posed by the latter and its negative effects on their families is non-negotiable. So, they put themselves in harm’s way, hoping against hope that they won’t contract the virus and/or bring it home to their loved ones.

Although we’re “in this together,” we have left many of the most vulnerable to fend for themselves. They live in food deserts and now have even fewer options at their disposal than before, as those with disposable income and time stocked up on supplies. They are disconnected from accurate, timely information, which is even more important as we learn new lessons about the virus daily. For some, their experience with this pandemic can best be described as “inconvenienced,” while others don the armor of homemade masks to preserve their (and our) lives.

My students are learning the same lessons many are starting to awaken to: when systems fail, the marginalized become more marginalized. The pandemic operationalizes the very definition of “disparities” that we discussed during the first lecture. We are all seeing that “differences rooted in social disadvantages that further expose individuals to additional disadvantage” mean that those who are the least equipped with the resources to withstand a pandemic are placed at higher risk of exposure, unable to effectively employ best-practices for protection against an unpredictable virus. The novel coronavirus has set the stage for a master class in health inequity and demands that we pay attention to the socially and racially stratified patterns emerging from the COVID-19 pandemic.  Luckily, experts have provided a game plan for helping the most vulnerable. Hopefully, this experience will build our empathy towards the overlooked among us as we tackle health inequity together.

Class is in session.

“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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COVID -19 and the clotting conundrum

Initially known as a predominantly respiratory disease, there is currently no doubt that COVID-19 is increasingly emerging as a prothrombotic condition. Observational studies, as well as published and anecdotal case reports have highlighted the thrombotic manifestations of COVID-19, with particular emphasis on the strong association between D-dimer levels and poor prognosis.1,2 While the COVID-19 clotting narrative has been dominated by venous thromboembolism (VTE) and pulmonary embolism (PE),3-5 macro-thrombosis of the coronary6 and cerebral circulations7 have also been reported, as have the prevalence of microthrombi arising from endotheliitis in other sites.8

The pathophysiology

Some authors have described this SARS-CoV-2 induced hypercoagulability as ‘thromboinflammation’, an interplay between inflammation and coagulability leading to sepsis-induced-coagulopathy (SIC) and disseminated intravascular coagulopathy in severe COVID-19 cases.9 The pathophysiology is still incompletely understood but may be largely explained by the three components of Virchow’s triad:

Endothelial dysfunction: SARS-CoV-2 virus enters the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is widely expressed not only in the alveolar epithelium of the lungs but also vascular endothelial cells, which traverse multiple organs.8 Varga, et al. reported this concept of COVID-19 ‘endotheliitis’ in their paper, explaining how endothelial dysfunction, which is a principal determinant of microvascular dysfunction, shifts the vascular equilibrium towards vasoconstriction, organ ischaemia, inflammation, tissue oedema, and a procoagulant state, leading to clinical sequalae in different vascular beds.8 Complement-mediated endothelial injury leading to hypercoagulability has also been suggested.10

Hypercoagulability: SARS-CoV-2-induced hypercoagulability has also been attributed as a consequence of the ‘cytokine storm’ that precipitates the onset of a systemic inflammatory response syndrome, resulting in the activation of the coagulation cascade.11,12 However, whether the coagulation cascade is directly activated by the virus or whether this is the result of local or systemic inflammation is not completely understood.12

Stasis: Critically ill hospitalized patients, irrespective of pathophysiology are prone to vascular stasis as a result of immobilization.13

Currently available data: predominantly observational studies

In some of the earliest data emerging from Wuhan, Tang, et al. reported significantly higher markers of coagulation, especially prothrombin time, D-dimers and FDP levels, among non-survivors compared to survivors of SARS-COV2 novel coronavirus pneumonia (NCP), suggesting a common coagulation activation in these patients.1

Subsequently, Zhou, et al., reported that D-dimer levels, along with high-sensitivity cardiac troponin I and IL-6 were clearly elevated in non-survivors compared with .14 This was highlighted in one of the earliest CCC-ACC webinars on COVID-19 in March 2020, by Professor Cao, who drew emphasis on their data where D-Dimer >1μg/mL was an independent risk factor for in-hospital death, with an odds ratio of 18.42 (p=0.0033). 14,15

In another single centre study among 81 severe NCP patients from Wuhan, Ciu, et al., observed that D-dimer levels >1.5 μg/mL had a sensitivity of 85% and specificity of 88.5% for detecting VTE events.3 In an observational study of 343 eligible patients by Zhang, et al., the optimum cutoff value of D-dimer level on admission to predict in-hospital mortality was 2.0 µg/ml with a sensitivity of 92.3% and a specificity of 83.3%.16

With a shift in the epicenter of the pandemic, data from Europe highlighted the prevalence of both arterial and venous thrombotic manifestations among hospitalized COVID-19 patients, many of whom received at least standard doses of thromboprophylaxis.5,13

Most recent data from an observational cohort of 2,773 hospitalized COVID-19 patients in New York, showed that in-hospital mortality was 22.5% with anticoagulation and 22.8% without anticoagulation (median survival, 14 days vs 21 days).17 Confounded by the immortal time bias, among others, these data underscore the pressing need for well-designed RCT’s to answer this burgeoning therapeutic dilemma.

Antithrombotic therapy: What is the guidance?

As physicians learn more about this clotting conundrum, there is an increasing need for evidence-based guidance in treatment protocols, especially pertaining to anticoagulation dosing and the role of D-dimers in deciding on optimum therapeutics.

International consensus-based recommendations published by Bikdeli, et al. in the Journal of American College of Cardiology on 15th April 2020 recommend risk stratification for hospitalized COVID-19 patients for VTE prophylaxis, with high index of suspicion.11 They further state that, as elevated D-dimer levels are a common finding in patients with COVID-19, it does not currently warrant routine investigation for acute VTE in absence of clinical manifestations or supporting information. For outpatients with mild COVID-19, increased mobility is encouraged with recommendations against the indiscriminate use of VTE prophylaxis, unless stratified as elevated-risk VTE.

The majority of panel members considered prophylactic anticoagulation to be reasonable for hospitalized patients of moderate to severe COVID-19 without DIC, acknowledging that there is insufficient data to consider therapeutic or intermediate dose anticoagulation; the optimal dosing however, remains unknown.11 Furthermore, extended prophylaxis, with low-molecular weight heparin or direct oral anticoagulants for up to 45 days after hospital discharge, was considered reasonable for patients with low-bleeding-risk patients and elevated VTE (i.e. reduced mobility, comorbidities and, according to some members, elevated D-dimer more than twice the upper normal ).11

A Dutch consensus published shortly after on the 23rd April 2020, also recommends prophylactic anticoagulation for all hospitalized patients, irrespective of risk scores.12 Imaging for VTE and therapeutic anticoagulation recommendations are largely guided by admission D-dimer levels and their progressive increase, based on serial testing during hospital stay, in addition to clinical suspicion. A lower threshold for imaging has been recommended if D-dimer levels increase progressively (>2,000-4,000 μg/L), particularly in presence of clinically-relevant hypercoagulability. However, in contrast to the consensus document published in JACC, the Dutch guidance recommends that, where imaging is not feasible, therapeutic-dose LMWH without imaging may be considered  if D-dimer levels increase progressively (>2,000-4,000 μg/L), in settings suggestive of clinically relevant hypercoagulability and acceptable bleeding risk.12

The need for RCT’s

Even as we scramble to clarify the pathophysiology, the urgency to establish evidence-based standard of care in terms of anticoagulation has never been greater. Dosing is a matter of hot debate (prophylactic versus intermediate versus therapeutic), especially considering the risk of bleeding that can arise from indiscriminate anticoagulation.

Furthermore, while we have data that underscores increased coagulation activity (D-dimers in particular) as a potential risk marker of poor prognosis, D-dimers remain non-specific and there is insufficient evidence as to whether they can be used to guide decision-making on optimum anticoagulation doses among patients with COVID-19.

The existing evidence on thrombotic complications and their treatment has been primarily derived from non-randomized, relatively small and retrospective analyses. Such observational studies have been hypothesis generating at best, and in the absence of robust evidence, randomized clinical trials are imperative to address this critical gap in knowledge in an area of clinical equipoise. And there are quite a few to watch out for, as evidenced by a quick search in Clinicaltrials.gov, some of which are already recruiting.

RCT’s of therapeutic vs prophylactic anticoagulation:

Currently recruiting at University Hospital, Geneva, this trial randomizes 200 hospitalized adults with severe COVID-19 to therapeutic anticoagulation versus thromboprophylaxis during hospital stay. The primary endpoint is a composite outcome of arterial or venous thrombosis, DIC and all-cause mortality at 30 days.

This open label RCT of hospitalized COVID-19 positive patients with a D-dimer >500 ng/ml is currently recruiting at NYU Langone Health (estimated enrolment of 1000 patients). Patients will be randomized to higher-dose versus lower-dose (e.g. prophylactic-dose) anticoagulation in 1:1 ratio. Primary endpoints include incidences of cardiac arrest, DVT, PE, MI, arterial thromboembolism or hemodynamic shock at 21 days and all-cause mortality at 1 year.

This randomized, open-label trial sponsored by Massachusetts General Hospital (MGH) commencing recruitment mid-May, will randomize 300 participants with elevated D-dimer > 1500 ng/ml to therapeutic versus standard of care anticoagulation in a 1:1 ratio, based on MGH COVID-19 Treatment Guidance. Designed to evaluate the efficacy and safety of anticoagulation, primary outcome measures include the composite efficacy endpoint of death, cardiac arrest, symptomatic DVT, PE, arterial thromboembolism, MI, or hemodynamic shock at 12 weeks, as well as a major bleeding event at 12 weeks.

  • Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients: Comparison of 40 mg o.d. Versus 40 mg b.i.d. A Randomized Clinical Trial (X-COVID 19)[https://clinicaltrials.gov/ct2/show/NCT04366960]

This open-label multi-centre RCT will recruit 2712 hospitalized COVID-19 patients in Milan, Italy, randomized to subcutaneous enoxaparin 40 mg daily versus twice daily within 12 hours after hospitalization, to assess the primary outcome measure of venous thromboembolism detected by imaging at 30 days.

 RCT of intermediate vs prophylactic dose anticoagulation:

A cluster-randomized trial of 100 participants, IMPROVE-COVID, sponsored by Columbia University will compare the efficacy of intermediate versus prophylactic doses of anticoagulation in critically ill patients with COVID-19. The primary outcome measure is the composite of being alive and without clinically-relevant venous or arterial thrombotic events at discharge from ICU or at 30 days (if ICU duration ≥30 days).

Even months later, COVID-19 continues to baffle clinicians. But what has been crystal clear right from the outset is that there is no alternative to evidence-based practice, and it stands true in the face of this clotting conundrum as well.

Image from Shutterstock

References

  1. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-847.
  2. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Apr 19. doi: 10.1111/jth.14859.
  3. Cui S, Chen S, Li X, Liu S, Wang F: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.. J Thromb Haemost. 2020 Apr 9. doi: 10.1111/jth.14830
  4. Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al. Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence. Circulation. 2020 Apr 24. doi: 10.1161/CIRCULATIONAHA.120.047430.
  5. Lodigiani C, Iapichino G, Carenzo L, Cecconi M Ferrazzi P, Sebastian T, et al., on behalf of the Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020; 191: 9–14.
  6. Dominguez-Erquicia P, Dobarro D, Raposeiras-Roubín S, Bastos-Fernandez G, Iñiguez-Romo A. Multivessel coronary thrombosis in a patient with COVID-19 pneumonia, European Heart Journal, , ehaa393, https://doi.org/10.1093/eurheartj/ehaa393
  7. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020 Apr 28.
  8. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418
  9. Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemost. 2020 Apr 17. doi: 10.1111/jth.14849.
  10. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases [published online ahead of print, 2020 Apr 15]. Transl Res. 2020;S1931-5244(20)30070-0. doi:10.1016/j.trsl.2020.04.007
  11. Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. J Am Coll Cardiol. 2020 Apr 15:S0735-1097(20)35008-7
  12. Oudkerk M, Büller HR, Kuijpers D, van Es N, Oudkerk SF, McLoud TC, et al. Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology. 2020 Apr 23:201629.
  13. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Apr 10. pii: S0049-3848(20)30120-1. doi: 10.1016/j.thromres.2020.04.013.
  14. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062.
  15. https://www.youtube.com/watch?v=CjEhV68GcD8&feature=youtu.be
  16. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, Zhang Z. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Apr 19. doi: 10.1111/jth.14859. [Epub ahead of print]
  17. Paranjpe I, Fuster V, Lala A, Russak A, Glicksberg BS, Levin MA, et al. Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19 [published online ahead of print, 2020 May 6]. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2020.05.001

“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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Innovations in 3-D and 4-D Technology in the Cath Lab

There have been tremendous advances in 3-dimensional (3-D) technologies in the past few years, not only in various medical and surgical fields but also in our daily lives outside of work; with more and more new features in cell phones, computer design programs, and movies!!  4-dimensional (4-D) imaging captures 3-D images over time. These technologies are particularly important in cardiology, especially in interventional cardiology. The heart is a very dynamic organ, and understanding the variation in the anatomy of vessels and geometry of cardiac structures is key to ensuring successful procedures, patient’s safety and good outcomes. More recently, newer innovations in both 3-D and 4-D technologies have been developed, so I decided to shed light on some of these innovations and how they can be potential game-changers in the cath lab.

  • 3-D Holograms

This technology was actually displayed at the Transcatheter Cardiovascular Therapeutics (TCT) 2019 meeting. It converts live transesophageal echo (TEE) imaging into real-time 3-D holographic video in the cath lab to aid structural heart procedures.  The 3-D hologram is projected on a special display screen, and the interventional cardiologist uses hand movements and a foot pedal/switch to change the image orientation without breaking the sterile field. It also allows the operator to see the tools they use in the cath lab, including catheters or devices, in real-time in a 3-D format. This technology does not even require the user to wear 3-D glasses! It was submitted for FDA regulatory review in September 2019.

  • HeartFlow Planner

This is a noninvasive, real-time virtual tool for coronary artery disease intervention. It allows interventional cardiologists to virtually map vessels on a 3-D coronary tree, with color codes indicating the fractional flow reserve-computed tomography (FFR-CT) values for each vessel as measured by a computational fluid dynamics algorithm. This seems to be a good tool for percutaneous coronary intervention (PCI) planning in vessels with significant disease; as it aims to provide us with a non-invasive way to determine whether a stenotic lesion if potentially flow limiting. However, it is important to note the CT-FFR has its own limitations, and some patients might still need invasive FFR for accurate assessment. This tool was approved by the FDA in September 2019.

Figure 1: 3-D CT-FFR coronary tree showing both flow limiting and non-flow limiting lesions [from reference 1].

  • 3-D Printing

3-D printing has been used in the surgical fields for more than a decade. It refers to making complex 3-D objects from computer-aided designs. This technology has been increasingly utilized in structural heart procedures in the past few years, where these 3-D models can be printed from a patient’s CT, magnetic resonance imaging (MRI), or 3-D ultrasound images (Figure 1). These 3-D printed structures not only help with procedural planning and device sizing but also allow operators to practice dry runs and perform pre-procedural navigation.

Figure 2: Image of a 3-D printed model which shows cardiac valves and major vessels with their geometric locations relative to each other (reference 3).

  • 4-D Imaging

4-D imaging adds an important component to 3-D imaging, which is the change of these 3-D images over time. 4-D flow images include the direction of blood flow, blood velocities and shear wall stress [2] (Figure 3). This is particularly important in coronary interventions, structural heart procedures and different congenital abnormalities where identification of blood flow in the 4-D view is useful, especially when the anatomy is complex. These changes in position over time help guide our procedures, not only to ensure successful outcomes but also to avoid potential complications. These 4-D images require large amounts of data, but they can be obtained from either cardiac MRI or computational fluid dynamics, which is a specialized area of mathematics and fluid mechanics in engineering [2]. 4-D imaging is still in its early phases, but it is another exciting advancement in our field.

Figure 3: Representation of an MRI-generated 4-D flow image showing blood flow through the aorta and major vessels (reference 4).

In conclusion, we have seen and continue to see tremendous advances in the innovations of 3-D and 4-D imaging with important implications in our work in the cath lab. With our continued collaboration with informational technology experts, engineers, and scientists, these innovations are potentially game-changers in different fields, including coronary interventions and structural heart procedures. I look forward to seeing how this technology continues to evolve in the coming decades!!

References:

  • Fornell, Dave “Overview of the top news and new technologies at the 2019 Transcatheter Cardiovascular Therapeutics meeting”, November 2019,

https://www.dicardiology.com/article/6-hot-topics-interventional-cardiology-tct-2019

https://www.itnonline.com/content/arterys-showcases-fda-cleared-4d-flow-mri-software-rsna-2016

“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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Wellness Amid a Pandemic

I think about wellness often and the unique aspects of being a physician that make preserving our wellbeing even more important. Of course, this COVID-19 pandemic has tested all of us and the things we turn to for wellness and our escape from medicine, may not be available to us right now. After work dinner and drinks, early morning group fitness classes, and young professional networking events have been replaced by Netlfix© and dine-in, home workouts, and Zoom “wine” downs. We all had to dig down deep inside to find new venues for wellness and if we were lucky, our institutions provided resources to help us during this crazy time. What this pandemic taught me was that there are things I still needed to work on to build my resilience even further- and I am totally okay with that. Working on ourselves to better ourselves should be a continuous goal- everyone has room for improvement.

As a single woman living in the city, my nights and weekends were always filled with social events. I felt very isolated and realized how much of my free time was being occupied by my friends and the events I attended as part of my wellness routines. I miss my morning classes at bootcamp and will never complain again when my alarm wakes me up at 4:25am to get to class- whenever that may be. Some of the things that have helped me are FaceTime and Houseparty dates with friends and family, walking outside on the few sunny days Boston has graced us with, trying to eat healthy when I can, in-home workouts which I am not a fan of to be completely honest, but most important, was being vulnerable with friends, family, colleagues, and even patients who asked how I was doing during our virtual visits. I met with a Wellness Coach provided through my institution and the lightbulb moment for me was when he reminded me to be kind to myself. I remember seeing posts all over social media about how we should be building businesses, getting in shape, writing grants, or checking off any other number of “goals” because we have “so much time” and feeling bad, but I got over that. In the middle of this crisis, all our lives have been disrupted, some much more so than others, and we are all doing the absolute best we can. I remind myself to be grateful and I started writing specific things down that I am grateful for each day.

May is Mental Health Awareness Month and as physicians, we shy away from talking about such things. It may be that we are supposed to be superheroes who are invincible, or it may be that if we did seek help and received a diagnosis we would have to declare it on some medical state licensing applications, or we may just be afraid. Mental health is one of the many aspects of overall wellbeing and there are many ways to reach out for help for those who need it. COVID-19 has had many casualties and we must guard our mental health during this pandemic. Find what works for you and do it. Reach out when you need to and remember that it is totally okay to not be okay. Protect your mind, body, and soul as these are key aspects of our overall wellbeing. I feel optimistic about our future. When we come out on the other side of this let us take all the lessons we learned and remember to never take things such as human contact for granted again.

Stay safe and stay healthy.

“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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COVID-19 Stage 2: Embracing Progress, Cautiously.

In these early days of May 2020, it seems like “change is in the air”. In the northern parts of this planet (myself based in Canada’s capital), winters’ cold, icy grip has thawed, and signs of nature and life are starting to be spotted everywhere. Of course, no mention of the year 2020 is complete without placing the Covid-19 pandemic in its proper context within the topic discussed. I’ve been seeing a lot of articles and discussions online that too easily link the “spring is upon us” and “life is getting back to its normal rhythm” ethos with the recent positive stories about Covid-19 infections. Reports of daily hospital admittance and mortality rates dropping are signs of progress indeed, specifically in nation states that were hit early and hard by the disease at the start of the year, and in the ensuing first few months.

While this is welcome and encouraging news, I can’t shake the feeling that people are either consciously or subconsciously paralleling the arrival of seasonal change, an end of the typical academic school year, and the learned attitudes of past years, onto what this 2020 calendar year will be like, moving forward from this stage. Undoubtedly, overall status of the Covid-19 pandemic is now changing, with factors like spread rate seemingly decreasing (in spots), knowledge about the virus increasing (everywhere), and local and national healthcare systems all working and adjusting to better handle the situation (with some exceptions). This, in addition to coordinated social, governmental and economical efforts, working in concert to prevent a much worse outcome from unfolding, all indicate advancement and positive aspects of where we stand at the moment, in early May of 2020.

                                                      (Image from pixabay.com CC-0)

However, and you knew I was going to bring up the “however” adverb! Equating what normally is the care-free, and bright-sunshine attitude of previous years to where we are this year, at this stage in the pandemic, is simply not appropriate and could be dangerous. There are still many unknowns about how SARS-CoV-2 may change with the seasonal transitions, not just within the northern hemisphere where we are coming out of winter and into spring and warmer weather, but also minding how will the seasonal changes affect the southern hemisphere, where the temperature changes go from warmer to cooler at this time of year. There are also questions remaining about how different cities and nations are implementing the various step-wise stages of coming out of the strict physical distancing parameters, which helped limit the size of the surge of infection. Will certain districts and cities experience a second wave of infectious spread? Will citizens be able and willing to go back into physical distancing status if needed? Those and many other questions are still left unanswered presently, and it’s too difficult to forecast with the limited data we have at this stage, in early May of 2020.

Having said that, I still want to bring back the sense of positive momentum we are presently experiencing. From a bird’s eye view point: We the people of this planet, united, are more informed, have a better handle over, and are able to deal with the Covid-19 crisis today much better than we were a couple of months ago. Together we can and will progress into the desired advantageous state of preparedness and better reaction to SARS-CoV-2 infection, and resulting disease, this is a fact. We just need to continue to investigate, learn, and plan appropriate steps to take, so that we can all safely reduce the dangers that still are posed by the virus, and take note and find ways to reduce the pain and loss that our communities have experienced so far, and moving forward. Only through those careful steps, and planning ahead, would we really feel like “spring is in the air”, and not a minute before then! Be safe, stay healthy, and care for one another.

“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 Importance of Maintaining the Public’s Trust in Science and Medicine

Often, and especially during the COVID-19 pandemic, there is a plethora of misinformation that is spread. We have all probably seen at least one scientific publication, news article, social media post, or YouTube video that is spreading information that is not accurate. Every day, I am bombarded by conspiracy theories or unfounded scientific claims while skimming through social media. During a time when information is rapidly disseminated through the internet, it is often difficult to extinguish a lie.

Sometimes, misinformation is inadvertently spread by well-meaning individuals who have not had the time or energy to confirm or critically appraise the information shared. “Liking”, “retweeting”, and/or sharing a post from a colleague/friend/relative is facile. We have all probably “retweeted” or shared certain articles and posts that we did not completely critically assess before sharing. Sometimes dissecting truth from fallacy is difficult, especially when information is disseminated widely. Our current technological advances with the internet and social media magnify opinions, good and bad. Occasionally, one may think, if multiple people I know and/or respect are sharing certain information and the number of posts about the false information outnumber those on the truth, then the misinformation must be true.

Occasionally, misinformation about science or medicine is shared by members of our own scientific and/or medical communities, which can sometimes be more damaging to our profession. For example, more assumed credibility may be given to a scientist or healthcare provider, even if his/her expertise is not in the area that is commented on. Conspiracy theorists may continually reference these “experts” to support their arguments. Sometimes, refuting incorrect information requires massive efforts but may never eliminate the long-lasting negative effects of the misinformation. For example, Andrew Wakefield’s infamous, now retracted scientific article that was published in The Lancet and falsely claimed an association between the measles, mumps, and rubella vaccine with autism is unfortunately still being referenced to support arguments against vaccinations even though multiple studies have overwhelmingly refuted the claims made in the retracted article.

With less malicious intent, some misinformation may be spread by the media or others in reference to research articles. Certain conclusions of research papers are sometimes not justified by the data presented due to inadequate sample size, biases, issues with the experimental design, etc. During a pandemic, since rapid dissemination of scientific and medical information is needed, there is frequently a tradeoff with the scientific rigor and reproducibility of the results. Since access to papers in preprint servers are available to the public, the media and public figures may tout certain research findings as truth when they have not been vetted by the peer-review process. A fellow AHA early career blogger, Dr. Allison Webel (@allisonwebelPhD), recently wrote an outstanding blog discussing the importance of the peer-review process (https://earlycareervoice.professional.heart.org/in-defense-of-peer-review/). Of note, even peer-reviewed articles are not free from research misconduct and incorrect conclusions. There are many articles retracted from high impact journals. Before the development of the internet and social media, critiques and feedback of research findings were typically only discussed at scientific meetings or at other selective venues (e.g., local conferences/presentations, journals typically not viewed by lay people, etc.). Now, these debates occur in the public arena with beneficial and negative aspects and frequently with nonexperts. These public debates may dilute the truth when unfounded comments are perpetuated.

What should we do about the spread of misinformation? Propaganda and false information are always going to be spread but we should try to mitigate their breadth and potential damage. On an individual level, researchers should thoroughly assess their results and determine whether their data are valid and whether the claims they make in publications are justified by the data before presenting the findings to the public. Limit overreaching conclusions. Scrutiny of results by authors and the research community is essential to the scientific process. Developments and advances in science often occur when findings are reproduced either within a specific lab/group or by other labs/groups and this is especially important to realize during a time when a deluge of single-center, small sample size papers are published about the COVID-19 pandemic. Dr. Elizabeth Knight (@TheKnightNurse), another fellow AHA early career blogger, recently calls to attention the scientific lessons learned from the current pandemic (https://earlycareervoice.professional.heart.org/evidence-whats-good-whats-good-enough-whats-dangerous-lessons-for-now-and-later/).

How do we influence other people’s opinions? Internal changes are often easier to make than changing other people’s opinions. However, we are all likely an influential source of information within our own social circles and networks. We may feel more comfortable directly communicating with people we know to correct misinformation. Altering the opinions of people who we do not personally know is more challenging. At minimum, as researchers and healthcare providers, we should not intentionally try to deceive the public. Flagrant dishonesty from researchers and/or healthcare providers may erode the public’s trust in our profession, possibly to a greater extent than a nonexpert’s comments. We all make mistakes and honest misunderstandings and misinterpretations can affect all of us. However, deliberately lying and abusing the influence of one’s position as a scientist or healthcare professional is more offensive. I do not know how best to address colleagues who blatantly mislead the public. If an individual we personally know is deceiving others, we can directly communicate with him/her about the impact of the misinformation. Depending on the extent of the damage created by an individual in our professional community who is propagating false information, should we review his/her ability to maintain as a member of our profession?

What are your thoughts on how we can preserve the public’s trust in science and 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.”