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Embolic Stroke of Undetermined Source: Current State of Evidence

Approximately 30% of all ischemic strokes are caused by an unknown etiology, also sometimes referred to as cryptogenic stroke1. Cryptogenic stroke has been defined as a cerebral infarct without a clear attributable etiology despite extensive vascular, cardiac and laboratory evaluations2. The possible underlying mechanisms for these ischemic strokes are varied and may include occult paroxysmal atrial fibrillation, paradoxical embolism with a patent foramen ovale (PFO), hyper coagulable state, non stenotic atherosclerotic disease.

A more recently coined term has been used to describe cryptogenic strokes which appear embolic on brain imaging: Embolic Stroke of Undetermined Source (ESUS). ESUS accounts for more than half of all cryptogenic strokes and has been defined as a cortical infarct without ipsilateral proximal arterial stenosis or a cardio embolic source3. Antiplatelet medications are generally used to prevent recurrent stroke in the absence of atrial fibrillation. However, clinical studies with long term cardiac rhythm monitoring have demonstrated a higher prevalence of atrial fibrillation in the cryptogenic stroke population4,5. With this background two clinical trials were initiated to investigate whether the direct oral anticoagulants were more effective than aspirin for secondary stroke prevention in patients with ESUS.

Results from the RESPECT-ESUS were presented at the World Stroke Congress in October 20186. The trial showed similar stroke rates with the two drugs at 19 months follow up; 4.8% per year with aspirin and 4.1% per year with dabigatran ( p=0.1 HR=0.85). The major bleeding events occurred at a similar rate with the two drugs- 1.4% per year with aspirin and 1.7% per year with dabigatran. Even though these results did not show a statistically significant difference, there is a slight indication of benefit in favor of dabigatran when patients are followed for long term. A post hoc subgroup analysis showed a statistically significant reduction in secondary stroke rates with dabigatran among patients older than 75 years.

NAVIGATE-ESUS7 trial was designed to compare rivaroxaban 15mg/day to aspirin 100mg/day in patients with a recent ESUS event. This was a multi-national trial which enrolled about 7000 patients who were then followed for a median time of 11 months after randomization. The trial was terminated early due to an increased risk of bleeding associated with rivaroxaban without a significant benefit of stroke risk reduction. Recurrent stroke or systemic embolism occurred at 5.1%/year in the rivaroxaban group as compared to 4.8%/year in the aspirin group. In the rivaroxaban group, there were 13 hemorrhagic stroke events as compared to 2 in the aspirin group. Major bleeding rates were also higher in the rivaroxaban group: 1.8%/year vs. 0.7%/year with aspirin.

An exploratory subgroup analysis was subsequently performed and the results were published earlier this month in JAMA Neurology8. The patients were stratified according to clinical characteristics predictive of atrial fibrillation including left atrial size and frequency of premature atrial contractions. Nine percent of the total trial population had a left atrial diameter size greater than 4.6cms. Among this prespecified group, rivaroxaban was associated with a 1.7%/year rate of recurrent ischemic stroke as compared to 6.5%/year with aspirin. This is a statistically significant difference in favor of rivaroxaban- hazard ratio =0.26, P=0.02. This result indicates that rivaroxaban may be beneficial in patients with ESUS who are found to have at least moderate enlargement of the left atrium as these are the patients most likely to have underlying occult atrial fibrillation.

While these results are promising, the findings need to be confirmed with a randomized clinical trial. This is the premise of the ongoing ARCADIA trial9 which will enroll patients with a recent ESUS event and evidence of atrial cardiopathy defined by specific ECG changes, serum biomarkers and left atrial dilatation. The patients will be randomized to receive apixaban 5mg twice daily or aspirin 81mg daily. The results of this trial will hopefully guide treatment decisions for this patient group in the future. In the meantime, based on the current evidence, a broad utilization of anticoagulants cannot be recommended for prevention of ESUS. Physicians should strive to monitor these patients with longer term cardiac rhythm monitoring techniques such as implantable loop recorders.

 

References:

  1. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol. 1989 Apr;25(4):382-90
  2. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35-41
  3. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet        2014 Apr;13(4):429-38
  4. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014 Jun 26; 370(26):2467-77
  5. Cryptogenic Stroke and Underlying Atrial Fibrillation. N Engl J Med 2014; 370:2478-2486
  6. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. N Engl J Med 2018; 378:2191-2201
  7. https://journals.sagepub.com/doi/full/10.1177/1747493018789543
  8. Recurrent Stroke with Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation: Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA Neurol. 2019 Apr 8
  9. The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods. International Journal of Stroke 0(0) 1–8

 

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Cardiac Intensivist – Just an Extension of an Interventionist?

Three pathways encompassing an intersection of the established subspecialties of critical care and cardiology have been proposed as a training framework for an aspiring ‘critical care cardiologist’ by the authors in a recent article1.  However, focusing specifically on the skill set outlined in the article,  a different and accelerated pathway for duly trained and interested interventionists may merit consideration.   With additional training in end of life/palliative care, intubation skills and advanced ventilator management a interventional cardiologist may likely fill the shoes in a modern ICU better than cardiologists from other subspecialties, including even those with additional critical care training.

Among the skill sets outlined in1, accredited interventional training likely prepares an individual to the greatest extent.  Issues of vascular access, sedation management and escalation of vasopressors for ‘crashing patients’ are daily routine in a busy catheterization suite.  Point-of-care ultrasounds (POCUS) should enhance the armamentarium of every thoughtful interventionist to identify regional wall motion abnormality and direct appropriate revascularization in area of myocardial dyskinesis/’stunning’. Additionally POCUS helps identify tamponade expediently,as well as potential advanced valvulopathy needing urgent invasive intervention. Pulmonary artery catheter insertion, monitoring of the hemodynamics, and management has gained resurgence in the era of valvular interventions and percutaneous mechanical circulatory support(MCS) for cardiogenic shock.  Post-procedure care for revascularized patients is one of the most important lesson for Fellowship trainees, as is early identification, and directed action in case of development of complications. Being integral to a heart team2 for complex decision making also allows contemporary interventional trainees to be involved in complex decision making, and working closely with the surgical team. With more patients requiring complex interventions in contemporary practice-often with need for atherectomy of a dominant coronary artery, and those with advanced conduction system disease-transvenous pacemaker placement is increasingly performed in the Cath Lab. Also pacemaker placement during transcatheter aortic valve replacements (TAVRs) forms an essential step of the procedure enabling deployment of the valve.  Assessment of managing patients with acute coronary syndrome including interpreting EKGs to identify hemodynamically significant arrhythmias emergently is definitely in the ‘day’s work’ for most interventional trainees,

When looking at structured training, the the COCATS 4 document3 has outlined some competencies for a budding cardiac critical care professional-and recognizes the importance of cath lab rotations in forming the foundation of solid procedural skills. The only skills outlined as those outside the realm of a general cardiology Fellowship were ‘Skill to place intra-aortic balloon pump emergently’-which most interventional trainees become competent at, and ‘Skill to perform endotracheal intubation’-which in most tertiary care institutions is done by anesthesia-and interventionists may acquire competency with additional training.

The Acute Cardiovascular Care Association (ACCA) of the European Society of Cardiology (ESC) have come-up with their own certification exam and a core curriculum4. In addition to the above, they have outlined need for identifying and appropriately managing renal dysfunction in critically ill patients. The focused interventional trainee gets ample exposure to preventing, identifying and treating acute kidney injury almost on a regular basis in this era of heightened awareness of limiting contrast, and contrast-sparing interventions. Also the document outlines the importance of early, aggressive and adequate treatment for pulmonary embolism(PE)-and most PE response teams across the nation are staffed and often led by an interventionist.

In summary, with additional training –interventional cardiologists, and those in-training, with appropriate interest should potentially be integral, and possibly in a leadership position in a critical care team of the future.

References:

  1. Miller PE, Kenigsberg BB, Wiley BM. Cardiac Critical Care: Training Pathways and Transition to Early Career. J Am Coll Cardiol. 2019 Apr 9;73(13):1726-1730.
  2. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. EuroIntervention. 2019 Feb 20;14(14):1435-1534.
  3. O’Gara PT, Adams JE, Drazner MH, et al. Journal of the American College of Cardiology May 2015, 65 (17) 1877-1886.
  4. https://www.escardio.org/static_file/Escardio/Education-Subspecialty/Certification/ACCA/Documents/ACCA_Core_Curriculum.pdf . Last accessed April 19, 2019.
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Cardiac CT: The Future of Diagnostic Cardiology?

As a medical student eyeing the field of radiology, the science of imaging of was all too seductive.  Ultimately, a love for cardiac physiology won me over, but an interest in imaging lingered.  As it turns out, cardiologists are part-time radiologists with expertise in a number of cardiac imaging modalities.

CT has become the latest frontier in cardiac imaging with a number of useful applications.

By now, coronary calcium scoring is a well-established tool for risk stratification in subclinical coronary artery disease.  Cross-sectional imaging is also useful for evaluating pericardial thickening in restrictive cardiomyopathy.  Beyond these traditional applications, newer techniques are poised to change the way we use CT to evaluate heart disease.

 

Coronary CT Angiography

Using fast, EKG-gated scanners, coronary CT angiography (CCTA) is a noninvasive means to detect coronary anomalies and obstructive plaque.  CCTA is a sensitive tool for excluding coronary disease, with a nearly perfect negative predictive value in the ACCURACY trial1.  However, specificity is poor and the presence of stents or calcium degrades image quality.

The specificity of CCTA is improved with FFR-CT (HeartFlow), a noninvasive method that mimics invasive fractional flow reserve measurements.  Computational fluid dynamics are applied to a 3D model of coronary anatomy in order to simulate the hemodynamic effects of stenotic lesions.  The PLATFORM trial2 showed how these technologies can safely reduce unnecessary catheterizations with no detriment to outcomes.

 

CT Myocardial Perfusion Imaging

CT myocardial perfusion imaging is also possible.  Indeed, a key advantage of CT is the ability to combine anatomic and physiologic evaluation in a single study.  However, exposure to radiation and iodinated contrast is an important consideration when comparing this to SPECT imaging.

 

As our diagnostic tools multiply, cardiac testing will become less invasive yet choosing the right study will become more complicated.  Cardiology is a fortunate field that controls much of its own imaging, but with the emergence of cardiac CT, we will need to collaborate with our radiology colleagues to push our fields forward in tandem.

 

References:

1Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 2008;52:1724-32.

2Douglas PS, Pontone G, Hlatky MA, et al. Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study. Eur Heart J. 2015;36:3359–3367. doi: 10.1093/eurheartj/ehv444.

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A Tale of Two Heart Attacks

Differentiation between Type 1 and Type 2 heart attack according to the condition of the coronary arteries (Thygesen, et al., 2012, Circulation)

Differentiation between Type 1 and Type 2 heart attack according to the condition of the coronary arteries (Thygesen, et al., 2012, Circulation)

Crushing. Stabbing. Gut-wrenching, knock the wind right out of you sort of pain in your chest, arms, neck, jaw or back.  This is how we commonly think of heart attacks and for patients and their loved ones – it is the worst of times. But just before the pain or discomfort starts, your body is adjusting to the cause of the heart attack and those causes can be classified as either Type 1 or Type 2 heart attacks. There are actually 6 types of heart attacks, but the vast majority of heart attacks, including those experienced by people living with HIV, are either Type 1 or Type 2.

A Type 1 heart attack is when a person has a sudden block in their blood flow, usually related to a blood clot that has broken off from a plaque, resulting in reduced oxygen going to the heart and death of heart muscle cells.  Whereas a Type 2 heart attack is when the heart needs more oxygen than it gets, due a number of potential causes including a spasm of the heart vessels, critical illness (including sepsis, very low blood pressure, and respiratory failure), or those undergoing surgery.

As I’ve previously written, HIV doubles the risk of heart disease and doubles the risk of having a heart attack. But in order to understand how to reduce this risk, we need to better understand what causes heart attacks in people living with HIV.  Building on previous work demonstrating that half of the heart attacks in people living with HIV are Type 2 heart attacks, Crane and colleagues recently presented new research on the differences in types of heart attacks among people aging with HIV. In over 27,000 adults living with HIV, the investigators determined the type of heart attack, probable cause of all Type 2 heart attacks, and looked at the rates of heart attack by age.

causes of type 2 myocardial infarction among people living with HIVThey identified over 1,000 Type 1 and 2 heart attacks and found that age was a primary predictor of the incidence and type of heart attack. Younger people with HIV had 10-fold more Type 2 than Type 1 heart attacks (although rates were low – only 22 heart attacks in this age group).  Starting in their 50’s, people living with HIV experienced significantly more Type 1 heart attacks than Type 2. Most interestingly were the heterogeneous causes of the Type 2 heart attacks including sepsis, respiratory failure, pneumonia, hypertensive emergency, and GI bleeds (Figure 1).

When asked what initially prompted this work, Dr. Heidi Crane from the University of Washington Center for AIDS Research states, “As an awareness of the importance of Type 2 heart attacks has grown in the general population, we were struck that there was so little data in people living with HIV- a population which has twice the rate of heart attacks as the general population.” This new study demonstrates that younger adults living with HIV are more likely to have Type 2 heart attacks from heterogeneous causes, which change the prevention strategies needed for this group.  While prevention strategies for Type 1 and 2 heart attacks require attention to traditional risk factors, we also need to pay attention to other non-traditional causes that may put someone with HIV at risk for heart attack due to supply-demand mismatch. Ultimately, these prevention strategies will need to be as heterogeneous as the causes. Dr. Crane continues, “There’s not going to be an easy fix for Type 2 heart attacks, there’s a lot going on and we will need to dive deeper to understand how to best tailor strategies to the individual patient.”

And yet, we’re often told that we need to treat the patient, not the disease. But in order to treat the patient, we have to know them, listen to them and understand the risk factors that they face as individuals for heart attacks. Whether it is a chronic disease like HIV infection or some other inflammatory condition, we will need to avoid the temptation to apply blunt prevention strategies, and favor the more challenging personalized solutions.

What are your experiences diagnosing and treating Type 2 Heart Attacks? How can we do a better job preventing them in people living with HIV and others at high risk? Tweet at me at @AllisonWebelPhD to follow the conversation.

 

Thumbnail photo credit: Photo by Kelly Sikkema on Unsplash

Thumbnail photo credit: Photo by Kelly Sikkema on Unsplash

 

 

 

 

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Right Ventricular Structure and Function

The effect of anticancer medication on the (LV) function and structure has been extensively investigated in comparison to the right ventricle (RV). In general, it’s known that deterioration of RV function is associated with significant morbidity and mortality. However, despite advancement in echocardiographic and other imaging techniques, the RV assessment remains challenging in comparison to the LV. In this short statement I will summarize some of the RV characteristics and distinguish

First: The right and left ventricles have distinct morphological difference. Embryologically, the RV is derived from the secondary heart field whereas the LV is derived from the primary heart field. The RV has crescentic non-ellipsoidal configuration and three anatomic divisions (an inlet region, trabeculae free wall/ apical region and an outflow tract). In addition, the RV mass and wall thickness is about 1/3 of the LV.1

Second: The RV has different cardiodynamics:

  1. The RV contraction is sequential and peristaltic: started by the RV inlet toward the trabecular free wall and end up with infundibulum. Rather than the LV contraction which is uniform, longitudinal and torsion. In case of RV volume or pressure overloads it’s become more uniform in contraction.
  2. The RV has 3 separate mechanisms of contraction:1
    1. Free wall inward movement “bellows – like effect) that is dependent on the moderator/ septomarginal band’s position and contractility.
    2. Contraction of longitudinal fibers (shortens long axis TV annulus toward apex)
    3. Traction of free wall from septal LV attachments.
  3. Shortening of RV is much greater longitudinally (75%) than radially (25%). The radius of the curvature and RV surface area do not change appreciably.
  4. The epicardial layer is mainly made with circumferential muscle and the endocardial is mainly made with longitudinal muscle loop. In comparison, the LV has helix that formed by ascending and descending obliquely oriented loops. Thus, twisting and rotational movements do NOT contribute significantly to RV ejection in compare to the LV.

Third: The RV surface/ volume ratio is high, therefore, a smaller free wall inward motion is required to eject the same amount of the LV stroke volume. Also, the RV isovolumetric contraction and relaxation are shooter than the LV, simply, because the pulmonary artery diastolic and RV filling pressure are low. In addition, about 30% of the RV systolic and stroke volume occur due to the interventricular septum (IVS) by the phenomena called “systolic ventricular interdependence.”1

Forth: Proper IVS position and contractile function are crucial for the RV function. The IVS function and curvature are modified in response to any pressure or volume overload. Under normal RV pressure, the IVS is concave toward the LV in both systole and diastole. However, in patient with pulmonary hypertension the IVS curvature become more convex shape which may help the RV to eject more blood against high pulmonary pressure.1,2

Fifth: RV failure occurs under almost two conditions, excessive RV afterload and IVS dysfunction. The most important determinant of the RV function is:1,2

  1. RV afterload (Vascular resistance and compliance)
  2. RV contractility (systolic function)
  3. The coupling of RV contractility to RV afterload
  4. Pericardial constraint/RV-LV diastole interactions

The RV function and structure assessment is challenging. An ideal index of contractility should be independent of afterload and preload, sensitive to change in inotropy, independent of heart size and mass, easy and safe to apply, and proven to be useful in the clinical setting.1,2 Invasively, the gold standard measure of RV function still the volume/ pressure relationship. The most clinically used measures of RV systolic function (RVEF, RV FAC, TAPSE, S’ tricuspid valve velocity, RV SV, strain and RVMPI) are load dependent. Just like the LV, we are slowly evolving into global longitudinal strain (GLS). Important to remember that LV GLS is a surrogate of LV ejection fraction (LVEF) and the dichotomy between the LVEF and GLS can be explained by global circumferential strain (GCS), (Figure 1).

Figure 1: Right ventricular structure and function

References:

  1. François Haddad, MD; Sharon A. Hunt, MD; David N. Rosenthal, MD; Daniel J. Murphy, MD Right Ventricular Function in Cardiovascular, Part I. Circulation 2008, 117:1436-1448
  2. François Haddad, Ramona Doyle, Daniel J. Murphy and Sharon A. Hunt. Right Ventricular Function in Cardiovascular Disease, Part II. Circulation 2008, 117:1717-1731

 

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QCOR19 Early Career Panel

 

Moderators and participants from the #QCOR19 Early Career Panel Discussion – Tell it to Me Straight: The Truth About Early Career. From left to right: Rashmee Shah, MD MS (University of Utah), John Spertus, MD MPH (University of Missouri – Kansas City), Umesh Khot, MD (Cleveland Clinic), Paul Muntner, PhD (University of Alabama at Birmingham), Karen Joynt Maddox, MD MPH (Washington University in St. Louis), and Faraz Ahmad, MD MPH (Northwestern University)

Moderators and participants from the #QCOR19 Early Career Panel Discussion – Tell it to Me Straight: The Truth About Early Career. From left to right: Rashmee Shah, MD MS (University of Utah), John Spertus, MD MPH (University of Missouri – Kansas City), Umesh Khot, MD (Cleveland Clinic), Paul Muntner, PhD (University of Alabama at Birmingham), Karen Joynt Maddox, MD MPH (Washington University in St. Louis), and Faraz Ahmad, MD MPH (Northwestern University)

 

The panelists sat at the front, ready to answer questions from the eager early career professionals (and mentors) in the audience. It’s the Early Career Panel at the Council on Quality of Care and Outcomes Research (QCOR) Scientific Sessions on Saturday April 6th in Arlington, Virginia.

The session moderators – Dr. Rashmee Shah from the University of Utah and Dr. Faraz Ahmad from Northwestern University – welcome the audience and thank the panelists, and flip on the projector.

Against a stark white background, the moderators present simple advice they’ve received in the past – good or bad – and ask the panelists to discuss.

The first one: “You shouldn’t negotiate the salary for your first job.” This discussion prompt starts an interesting conversation – touching on topics not typically addressed in early career salary negotiation tips.

In terms of first-year faculty positions, Dr Paul Muntner, Associate Dean of Research at the School of Public Health at University of Alabama at Birmingham, points out that equity comes into play. No matter where you go, first-year faculty make similar salaries. That doesn’t mean you can’t negotiate for other things though. In fact, some other benefits may be worth more than an extra $1-2k in salary. For example – funding to covering moving expenses, protected research time, statistical support, and access to certain databases are some of many aspects of your new job (to be) are all things to consider.

Dr Umesh Khot, from the Cleveland Clinic, chimes in that drafting a “Letter of Understanding,” outlining the extras in your job packet and what your responsibilities will be, is an important document to have. For the clinicians in the room, protected time for research and covering for colleagues in clinic were two major topics. Having a supervisor who values your time in research means should you be called on to cover in clinic for someone way at a conference, that time will be made up to you. Should anything not live up to the discussion as you start your new job, you’ll have something concrete to reference.

Dr. John Spertus, from the University of Missouri – Kansas City, was the first to bring up salary gaps in the context of salary negotiation. Per Pew Research Center, race/ethnicity earning gaps are narrower in the STEM workforce than non-STEM, but more importantly to me, they still exist. Among those who work in STEM jobs, blacks earned 81% as much as whites and those of Hispanic ethnicity earn 85% as much as whites. A survey in the United Kingdom and Europe found that women working in STEM jobs earned a fifth less than their male colleagues, and that the gap between men and women increased with age and experience. In the US, an 11% difference was observed, though it’s considered a conservative estimate. Dr. Karen Joynt-Maddox touched on the idea of salary gaps, pointing out that after the K-level (referring to the early career NIH grant mechanism), salaries diverge greatly. “There is less anchoring for equity later on,” she said, “so it’s very important to negotiate.”

One of the biggest challenges in closing the wage gap on the individual level is knowing what your more-advantaged colleagues are making. In contrast to non-academic fields, we may be at an advantage. For public institutions, including universities, all salaries are published online. Prepping for your salary negotiation by doing your research first will give you an idea of the salary ceiling for your goal position. You can use resources like IBHE, The Buckeye Institute, and Chronicle to look up salaries.

What’s the best early career advice you’ve received? What do you wish you had known when you started out?

 

Follow the Early Career Panel moderators and participants on Twitter:

Rashmee Shah, MD MS (@RashmeeUShah)

Umesh Khot, MD (@UmeshKhotMD)

John Spertus, MD MPH (@JSpertus)

Karen Joynt Maddox, MD MPH (@KEJoynt)

Paul Muntner, PhD (@MuntnerPaul)

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Referral Letter

A typical referral letter arrives in my tray:

A 55-year-old diabetic female noticed pain and discoloration of the right foot for several days.

 

Immediate admission was arranged for this patient:

A junior resident presents the case. She has clerked the patient and filled all the necessary forms and ticked all the necessary boxes. Everything is dated and signed appropriately. Her ankle brachial index is 0.7 on the right and 1.1 on the left. The patient falls in a Rutherford Class IV. With such thorough documentation, we were ready to pay the patient a visit and consent her for the planned peripheral angiogram and revascularization. This resident rounds with me every day and has clearly understood the process of consenting: procedural steps and complications included. I told my resident that I appreciate her energy and proactivity. I was so proud of her and thought “Hmm very little left for me to teach this young lady”. So, we walked over to the patient’s room to meet her and her family.

 

We enter the patient’s room:

My resident starts introducing the patient to me and recapping her history. In the meantime, I look at my patient from a distance. I immediately notice the anxious look. Perhaps she’s nervous about her foot and a possible amputation. I also notice how thin she is. Something doesn’t add up.  Diabetes is on the rise worldwide. Most of our poorly controlled diabetics who present with peripheral vascular disease have other end organ damage like some nephropathy or retinopathy. Most are overweight. She has none. I flip the chart in my hand and notice that her HbA1C is 7%. I ask about her weight loss. “It’s all very recent”, she says. I ask about other constitutional signs and she states there are none. She also has had no history of claudication. This doesn’t sound like long standing atherosclerosis. I approached her to examine her. I held her hand for the first time to feel her pulse. Oh, the lost art of a physical examination..Why examine her when her peripheral vasculature will be defined by a CTA and all the boxes in the chart are ticked?  The answer was right there: she was in atrial fibrillation. I glance at her EKG and sure enough she is in atrial fibrillation. Her hands told me more. She was sweating and had a tremor. I knew at this point what I needed to teach my resident. Medicine is so vast and so integrated. We cannot presume cardiovascular diseases and endocrine disorders are not interrelated. After all, this patient needed an endocrinologist.

 

Later that day she was taken to the cathlab:

Her TSH was high. Her transesophageal echocardiogram confirmed a left atrial thrombus. We discussed acute limb ischemia with the endocrinologist. We administered B blockers and obtained a consent for the procedure. Her angiogram revealed a thrombus at the right tibioperoneal trunk. Instead of whipping out the QuickCross microcatheter and GlideAdvantage wire, I performed manual aspiration of the thrombus. Fortunately, flow was restored almost immediately. The Society for Vascular Surgery and the North American Chapter of the International Society of Cardiovascular Surgery created a classification that ranged from non-threatened extremity, threatened extremity to finally ischemia with no possible salvage in 2002. Timely intervention is warranted in salvageable cases. Fogarty established surgical thromboembolectomy as the standard of care in the 1960s. Dotter introduced thrombolysis in the 1970s which evolved to current day catheter directed thrombolysis and aspiration. Both surgical and catheter directed thrombectomy have been studied. Theodoridis et al published a review article that indicated the technical success rate of endovascular techniques reaches 79.3%. A second procedure was required in 77.8% of those enrolled. The overall complication rate was 28.7%. Novel techniques that combine catheter directed low dose thrombolysis with and without mechanical thrombectomy have also been evaluated and found to be largely comparable.1-3 Procedural questions related to my patient were confined to the following:

  1. Use of a distal protection device: Trials have demonstrated a wide variation in the rate of distal embolization. This wide range is explained by the different lesion types, lengths, treatment modalities. The highest rate is in those with TASC C and D lesions, acute and subacute presentations, and with the use of atherectomy devices.4-10 However, major adverse events and amputations rates have not been significantly reduced with the use of distal protection devices.
  2. Use of an infusion catheter is usually reserved for cases where adequate flow and removal of thrombus is inadequate.

 

Upon returning to her room, there was more to discuss:

Her thyrotoxicosis was under investigation and control. Her atrial fibrillation needed to be addressed at this point. She needed rate control until she becomes euthyroid. With a thrombus in her left atrium and embolization to her lower extremity, she needed anticoagulation. The choice of an agent is another lesson for another day.

The resident and I walked out of her room with a sense of satisfaction. Both of us learned something that day. A patient is more than a referral letter..much more.

 

REFERENCES:

  1. Shrikhande GV, Khan SZ, Hussain HG, et al. Lesion types and device characteristics that predict distal embolization during percutaneous lower extremity interventions. J Vasc Surg2011;53(2):347–52.
  2. Shammas NW, Shammas GA, Dippel EJ, et al. Predictors of distal embolization in peripheral percutaneous interventions: a report from a large peripheral vascular registry. J Invasive Cardiol2009;21(12):628–31.
  3. Mendes BC, Oderich GS, Fleming MD, et al. Clinical significance of embolic events in patients undergoing endovascular femoropopliteal interventions with or without embolic protection devices. J Vasc Surg2014;59(2):359–67.e1.PMCID: PMC4492297
  4. Shammas NW, Coiner D, Shammas GA, et al. Distal embolic event protection using excimer laser ablation in peripheral vascular interventions: results of the DEEP EMBOLI registry. J Endovasc Ther2009;16(2):197–202.
  5. Karnabatidis D, Katsanos K, Kagadis GC, et al. Distal embolism during percutaneous revascularization of infra-aortic arterial occlusive disease: an underestimated phenomenon. J Endovasc Ther2006;13(3):269–80.
  6. Shammas NW, Dippel EJ, Coiner D, et al. Preventing lower extremity distal embolization using embolic filter protection: results of the PROTECT registry. J Endovasc Ther 2008;15(3):270–6.
  1. Rheolytic Pharmacomechanical Thrombectomy for the Management of Acute Limb Ischemia: Results From the PEARL Registry. Leung DA, et al. J Endovasc Ther. 2015
  2. Acute on chronic limb ischemia: From surgical embolectomy and thrombolysis to endovascular options. de Donato G, et al. Semin Vasc Surg. 2018
  3. Thrombolysis in Acute Lower Limb Ischemia: Review of the Current Literature. Theodoridis PG, et al. Ann Vasc Surg. 2018.
  4. Comparison of Low-Dose Catheter-Directed Thrombolysis with and without Pharmacomechanical Thrombectomy for Acute Lower Extremity Ischemia. Gandhi SS, et al. Ann Vasc Surg. 2018.

 

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Preventive Cardio-Oncology: The Rise of Prehabilitation

Figure 1 Prehabilitation: optimization of overall health, wellness, and fitness prior to initiation of therapies that might adversely alter fitness, strength, quality of life, or function.

Figure 1 Prehabilitation: optimization of overall health, wellness, and fitness prior to initiation of therapies that might adversely alter fitness, strength, quality of life, or function.

As I near the end of my job search process and prepare to review offers and sign a contract, it is absolutely incredible to me to consider that I am completing training at just the right time for me in cardiology. While sitting in a preventive cardiology team room, I overheard two exercise specialists describing a project that they plan to present in several weeks at a national conference. I overheard them use the word ‘prehabilitation’. While the word is not brand new in their professional world or even in cardiology, at that time the word was novel to me. I felt excitement rise within me as I recognized the word ‘prehabilitation’ as a concept that I have envisioned for quite some time to be key to what I would like to achieve and develop in the emerging field of preventive cardio-oncology. As a senior cardiology fellow, my training has been particularly enriched in cardio-oncology (see CardioOncTrain.Com), preventive cardiology, heart disease in women, and precision medicine. I plan to have a heavy emphasis on prevention in my practice, and with eventual incorporation of maturing tools in precision medicine. If you too are interested in preventive cardiology and cardio-oncology, you may want to consider a combined practice of preventive cardio-oncology.  If you are also interested in heart disease in women, then you may want to consider preventive cardio-oncology particularly in women, e.g., women with breast cancer.  Yes, that is quite focused, but can be an incredible niche.  Yet, let us take a step back from the idea of preventive cardio-oncology in breast cancer or any other cancer and first consider how far we have come in the broader field of cardio-oncology.

In the burgeoning field of cardio-oncology, one could argue that we are doing quite well as a community with epidemiology and management of cardiovascular toxicities from cancer therapies. Our ability to completely predict cardiovascular toxicity in individuals is still in progress. Nevertheless, the field has come so far regarding what we now understand about pathophysiology, risk factors, and incidence of cardiovascular toxicity. In particular, due to the continuous and rapid innovation in cancer therapies, cardio-oncology continues to grow exponentially. If you are interested in or planning to join the field, now is a great time!

While the main focus in cardio-oncology has been on secondary and tertiary prevention of cardiovascular toxicity and its sequelae, an era is approaching that may focus even more so on primordial and primary prevention of cardiovascular toxicity. What if we could figure out ways to prevent cardiovascular toxicity before it even happens? What if we can even avoid development of risk factors themselves? These two questions point towards a focus on primary and primordial prevention, respectively. Indeed, for decades we have been focusing largely on secondary and tertiary prevention in Cardio-Oncology. Perhaps it is now time to focus more on what would appropriately be termed preventive cardio-oncology, a merger between preventive cardiology and cardio-oncology.

A hallmark of preventive cardiology has long been cardiac – and in fact cardiopulmonary – rehabilitation. This usually would occur in the setting of secondary or tertiary prevention. As such, ‘rehab’ generally has at least a few purposes. One purpose is to help individuals get back to the level of cardiopulmonary function they had prior to their cardiovascular event. A second purpose is to actually optimize their cardiopulmonary function, regardless of their original preexisting starting point, and help them develop a sustainable lifestyle modification program that can hopefully help prevent another event. A third purpose is to provide support and camaraderie that can help individuals regain the confidence they need to develop and maintain heart healthy lifestyle habits, by knowing they’re not alone in the process. For young patients, such as young adult women with spontaneous coronary artery dissection, this third purpose can be particularly beneficial.

Studies are now showing that cardiopulmonary rehab can also be useful in patients who have completed cancer therapy – in a sense as their ‘event’1,2. This is in part because cancer therapies can impact the heart, vasculature, and lungs, as well as other organ systems. In addition, while undergoing therapy for cancer, individuals often tend to lose fitness, energy, strength, and motivation for lifestyle modification, which is entirely understandable. Studies are therefore also showing that individuals who pursue exercise in the form of ‘habilitation’ while undergoing cancer therapies will also often have improved fitness and cardiovascular function and outcomes following the completion of therapy1,3.

Notably, newer studies are suggesting that exercise prior to the initiation of cancer therapies can further improve fitness, strength, quality of life, and cardiovascular function during or upon completion of cancer therapy1,4. This concept of ‘prehabilitation’ is catching on and will most certainly become a centerpiece and hallmark of primary prevention and perhaps even primordial prevention of cardiovascular toxicities.

Essentially, we need to recognize the impact and power of hysteresis, which suggests that the cardiopulmonary fitness starting point for a patient diagnosed with cancer will determine their cardiopulmonary fitness endpoint after treatment for cancer. This of course is intuitive, but not usually the focus early on in cancer survivorship. Since one in three individuals develop cancer in their lifetime5, it would be reasonable to recommend that all individuals optimize their cardiopulmonary fitness and prioritize lifestyle modification to ensure a desirable cardiopulmonary starting point if ever one is unfortunately diagnosed with cancer. If we take a step back, we realize that is quite similar to the argument for optimizing cardiovascular health in the general population. One in three individuals dies from cardiovascular disease each year6. It is therefore reasonable to recommend that all individuals optimize their cardiovascular health and prioritize lifestyle modification to hopefully help avoid cardiovascular events. When we view (i) cardiopulmonary fitness after cancer therapies and (ii) cardiopulmonary fitness associated with cardiovascular health in the general population through similar lenses, it becomes clear that preventive cardiology and cardio-oncology could potentially come together in an emergent subspecialty of preventive cardio-oncology.

For all individuals, the overarching goal is optimal cardiovascular health based on life’s simple seven: diet, physical activity, obesity, cholesterol, diabetes, blood pressure, and cigarette smoking, in the context of non-modifiable and also nontraditional modifiable risk factors. For individuals with cancer, who become survivors at the moment of diagnosis7, additional goals are preserving  strength, endurance, quality of life, and function.

To achieve long-lasting success in preventive cardio-oncology, we will need to consider three Ps: protocols, partnerships, and payments. In this hot new field of preventive cardio-oncology in which you and I might be trailblazing, together we need to develop standard protocols that can be used across the nation – and in fact across the world – to provide the best care for our patients. We will need Scientific Statements and Guidelines as the backbone of our practice. To facilitate evidence-based prevention, we will need a combination of retrospective, cohort, and case studies, as well as clinical trials. We will need to be sure to practice team-based care and forge lasting partnerships among clinicians, exercise specialists, and others in order to guide patients along gentle, individualized pre-habilitation, habilitation, and rehabilitation care plans. Importantly, relevant payment structures will need to be developed and adequately compensated by government, state, and private insurance.

An exciting path is before us Early Career folks in preventive cardio-oncology, as we shape the opportunity to practice in cardio-oncology from the perspective of primordial, primary, secondary, and tertiary prevention in women and in everyone.

 

References

  1. SquiresRW, Shultz AM, HerrmannJ. Exercise Training and Cardiovascular Health in Cancer Patients. Curr Oncol Rep. 2018 Mar 10;20(3):27. doi: 10.1007/s11912-018-0681-2.
  2. Lee K, Tripathy D, Demark-Wahnefried W, Courneya KS, Sami N, Bernstein L, Spicer D, Buchanan TA, Mortimer JE, Dieli-Conwright CM. Effect of Aerobic and Resistance Exercise Intervention on Cardiovascular Disease Risk in Women With Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2019 Mar 28. doi: 10.1001/jamaoncol.2019.0038.
  3. https://journals.lww.com/oncology-times/pages/articleviewer.aspx?year=2019&issue=02050&article=00014&type=Fulltext. Accessed April 4, 2019.
  4. https://www.acc.org/about-acc/press-releases/2017/03/08/14/42/history-of-exercise-helps-prevent-heart-disease-after-breast-cancer. Accessed April 4, 2019.
  5. https://www.cancer.org/cancer/cancer-basics/lifetime-probability-of-developing-or-dying-from-cancer.html. Accessed April 4, 2019.
  6. https://professional.heart.org/idc/groups/ahamah-public/@wcm/@sop/@smd/documents/downloadable/ucm_503396.pdf. Accessed April 4, 2019.
  7. Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL, Bandera EV, Hamilton KK, Grant B, McCullough M, Byers T, Gansler T. Nutritionand physical activity guidelines for cancer survivors. CA CancerJ Clin. 2012 Jul-Aug;62(4):243-74. doi: 10.3322/caac.21142.

 

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The Emergence of The Field of Cardio-Oncology

By 2026, it is anticipated that there will be more than 20 million cancer survivors in the US1. The increase in prevalence of cancer survivors is largely due to discovery and implementation of effective chemotherapeutics and radiation therapy.  This success has come with a price, however, as the same chemotherapeutics and radiation therapy that cure cancer also damage vital organs, such as the heart. A wide range of chemotherapeutics have been associated with coronary artery disease, pericardial disease, and thromboembolic disease. Radiation therapy may accelerate premature atherosclerosis through acute inflammation leading to early vasculopathy in irradiated regions. With the introduction of each effective novel agent in treatment that prolongs survival,  side effects may  affect patient health and quality of life.

These factors have prompted the newly published AHA Scientific Statement on the field of Cardio-oncology, focused on the vascular and metabolic ramification of cancer treatment2. Cardio-oncology is a rapidly growing field of study given the prevalence of cancer and the need for physicians to address the unique challenges of treatment of cardiovascular disease in the cancer population.

Similar to general cardiology, prevention is a vital aspect of the field of cardio-oncology. This is due to the fact that both detection and treatment of cardiotoxicity is difficult. Symptomatically, cardiotoxicity can take years to manifest with the use of certain chemotherapeutics  and detection of subclinical cardiotoxicity is challenging. Thus, monitoring and screening become the most effective ways to minimize risk of development of cardiotoxicity and vascular complications.

Care in the cancer population should be multi-disciplinary from the moment the decision is made on the chemotherapeutics/radiation cycle to be used in treatment. Oncologist, cardiologists, and primary care physician are a vital part of care and must work together to make sure patients are medically optimized before start of treatment regimens. This includes thorough risk stratification and analysis of the benefits of treatment modalities, which needs to be individualized. Demographic factors such as the patient’s family history, prior cardiac history, current exercise tolerance are important factors to consider. Identification of patients at high risk would allow for consideration of alternative therapy, closer monitoring, screening, and possibly prophylactic treatment with cardioprotective medications. These patients can be monitored closely and undergo regular screening for signs of ventricular dysfunction.

Cardio-oncology is an exciting field of study with many unanswered questions. As literature continues to grow, I hope that we can meet the many challenges of cancer treatment.

 

References:

  1. Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. 2016. Cancer treatment and survivorship statistics. CA: A Cancer Journal for Clinicians 66 271–289.
  2. Campia U, Moslehi JJ, Amiri-kordestani L, et al. Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association. Circulation. 2019;139(13):e579-e602.

 

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Glossophobia: How To Tackle Your Fear of Public Speaking

This year at #ExperimentalBiology2019 my abstract was selected for oral presentation in the “Environmental and Epigenetic Contributions to Disease Origin” session, sponsored by the Water and Electrolyte Homesostasis Section of the American Physiological Society. When I received the email stating that my abstract was selected I, initially, was super excited. This was huge news – my first oral presentation in graduate school!

However, shortly after, the realization of speaking in front of people hit me and glossophobia, the fear of public speaking, quickly washed over me. The conference was months away, yet, there I stood, frozen, with the anxiety of presenting my work in front of a large group of people. What was I going to do?

Being able to effectively translate your science to a population who doesn’t know your work is something, as scientist, we all have to do. Proper communication is important because during this time, you can receive good feedback or questions that have the potential to propel your research to the next step. So, it was very crucial for me to make sure that I delivered an effective presentation.

Fast Forward to the day before my presentation and I finally have down the perfect delivery. However, the big problem now is making sure that I can stay calm enough to deliver as I have practiced. Very often, during the practice presentations with my advisor, I would become so nervous that I would either speed through the entire presentation, do not explain my presentation well, or a combination of both. At one point she even asked where I would like her to sit during the presentation so that I did not see her and become extremely nervous (during the actual presentation she sat in the back and remained crouched the entire time so that I couldn’t see her). So, what do you do when you have practiced your presentation almost a million times and are still overwhelmed with anxiety?

When trying to determine how to attack my anxiousness, these are a few tips that I found useful:

  1. Take a deep breath. You have spent a lot of time preparing for this day, you got this!
  2. No one knows your material like you do. You have spent plenty of hours and weekends trying to answer your particular research question. There is no one in the audience (besides your advisor) who will know your research like you do.
  3. Focus on the material and not the audience.
  4. Channel your nervous energy and make it work in your favor. For me, after I finished the introduction slides and realized that this was not as bad as I had thought. I was able to channel all of my energy into my excitement for my research. This was cool data that I was sharing and I wanted the audience to be just as excited about it as I am.
  5. Visualize your success.

 

What other tips can you think of that can help people with glossophobia overcome their fear?