CardioNerds (Amit Goyal and Daniel Ambinder), Dr. Victoria Thomas (Cardionerds Ambassador, Vanderbilt University Medical Center), and Dr. Quentin Youmans, cardiology fellow at Northwestern Medicine Bluhm Cardiovascular Institute, join Dr. Clyde Yancy, Vice Dean for Diversity and Inclusion and Chief of Cardiology in the Department of Medicine at Northwestern for an important discussion about underrepresentation in clinical trials and guidelines. This episode was recorded during a live event hosted by the ACC Illinois Chapter. Listen in to hear why diversity matters in clinical trials, how we can recruit more minorities in representation in CV trials and so much more! Stay tuned for a message by chapter Governor, Dr. Annabelle Volgman.  

The PA-ACC & CardioNerds Narratives in Cardiology is a multimedia educational series jointly developed by the Pennsylvania Chapter ACC, the ACC Fellows in Training Section, and the CardioNerds Platform with the goal to promote diversity, equity, and inclusion in cardiology. In this series, we host inspiring faculty and fellows from various ACC chapters to discuss their areas of expertise and their individual narratives. Join us for these captivating conversations as we celebrate our differences and share our joy for practicing cardiovascular medicine. We thank our project mentors Dr. Katie Berlacher and Dr. Nosheen Reza.

Audio editing by CardioNerds Academy Intern, Dr. Gurleen Kaur.

Video Version • Notes • References • Production Team

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Video version

https://youtu.be/5gGqWysdCT0

Show notes

1. Why does diversity matter in clinical trials?

Having clinical trial enrollment being representative of the general population in which we practice is essential for the generalizability of the trial results.Representative populations matter so we can say to patients, “yes, there were patients that think like you and look like you in the trial.” We can confidently tell them how patients within the trial have done. This is important when we are trying to narrow health disparities to provide confidence and comfort to our patients.Advocacy for health equity is important but not enough. We need data or evidence to support why a change in our behaviors and clinical practice is needed. An evidence base that reflects and includes all our patients is key to bridging health disparities.In medicine, the case for diversity also includes to better serve diverse patients, to promote health equity, to provide diverse mentors at all levels, to bring different points of view to debates and problem solving, to better engage our communities, and to include investigators with a broad range of perspectives in their scholarly activities. (1)

2. How do we recruit more minorities in representation in cardiovascular trials?

We need more advocates for diversity in trials in the room when the conversations about trial designs are being made. This is why diversity of leadership is important.There needs to be an intentional approach for every clinical trial to recruit people that are likely to be candidates for enrollment.Stop asking patients to come “downtown” but instead go to their town or their communities. Meet them where they are.Always make sure you are providing some additional advantage or opportunity for the patients you have recruited into your trials. Don’t make it a one-way street. Allow patients to feel that they are getting the best care and generate trust with them.To gain trust, try to get a sense of what is happening in your patient’s life. Find 2-3 minutes to ask them to give a mini biography of their lives. This goes for routine clinical care as well as conducting trials!

3. What advice do you share with people who are underrepresented in medicine, and who may potentially face racism or sexism?  

You have two choices when people promote division and hatred. You can choose to be angry, or you can choose to not let others’ poor decisions or thoughts define you.Your best tool as UIM is to control yourself and to be successful.Remember that your uniqueness can make a difference in the lives of so many others. It can help you execute making a large impact for so many more people.

4. How do we recruit more diversity in medicine or cardiology in general?

One strategy is to establish new medical school(s) at Historically Black Colleges or Universities (HBCUs). HBCUs recognize broad talent, refine that talent, and propel that talent to success.The current 4 medical schools in part aligned with HBCUs and serving Black medical students represent 2.6% of total medical schools yet account for 15% of all Black medical students. (2)We must stop looking at diversity as a “representativeness” cause. We should all be striving for excellence. To achieve this, we need diversity of thought, diversity of ideas, and diversity of execution. This will not be accomplished if we continue all have the same “skin”.There must be intentionality for diverse leadership. There needs to be diversity in the C-suite of hospitals and the Dean’s executive committee of medical schools.  Diversity in medicine will follow suit when there is a diverse thought process in those rooms that affect the future.

5. How has structural racism affected studies and guidelines?

There has been a system in medicine early on in our country that intentionally separated people as a function of race such as the “Jim Crow experience”. This disabled many opportunities for certain groups of people.Physicians must recognize there are still residual consequences of the Jim Crow experience that have allowed for a “cultural set point” that continues to be operative today. (3)The “cultural set point” has allowed many generations to become acculturated subconsciously to believe there are distinct differences between people and then behave accordingly that leads to effect of how one may practice medicine.

6. How do we combat structural racism within cardiology or medicine?

If you are trying to incite culture change, something abrupt likely will need to happen. You must embrace and enjoy the need for change.CardioNerds and the new generation of physicians have the license to be architects of the future in medicine. We have the power to change the culture as we practice and develop new studies and guidelines.Consider a positive disruptive change when making new ideas for the future in medicine to battle social injustices within medicine.We must fundamentally change the way we do things to change our already known processes.

7. Should there be race or gender-based guidelines or socioeconomic status guidelines?

The first step is recognizing this is a complex issue and when one is developing a trial there needs to be a thoughtful conversation.We do need more data in the study of racial and gender differences.We still need race and gender-based research – not race/gender-based research looking for a different biology, but research trying to unravel where do we see these differences that are otherwise inexplicable, with the exception of bias. (4)

8. How to get your peers and patients to trust you to advocate and promote diversity, equity, and inclusion?

Per Dr. Yancy you need 3 traits to become a strong and effective advocate: Competency: to strive to be best physician you can be and to give the best care you can. You need your voice to be respected.Civility: be able to stand in a room where there is a difference of opinions and hold yourself appropriate. Manage to have eye contact, manage your emotions, because remember if you allow people to make you angry and show it then they have won.Compassion: show people that you genuinely care.  Remember you may have had opportunities that your patients or colleagues may never have had.

Also remember to go back to evidence! The evidence is there to promote for more diversity within the physician workforce. This in turn leads to diversity of thought, ideation, and execution which help improve clinical trial subject representation.Remind people that in the 2019-2020 academic year, 21,863 first-year medical students were enrolled in the US, of whom 1,626 were Black—a number that has been stagnant since 1978.

References

Douglas, P. S., Williams, K. A., & Walsh, M. N. (2017). Diversity matters.Association of American Medical Colleges. Facts: Applicants, Matriculants, Enrollment, Graduates, MD-PhD, and Residency Applicants Data. Published 2020. Accessed December 3, 2020. https://www.aamc.org/data-reports/students-residents/report/factsYancy, C. W. (2020). COVID-19 and African Americans. Jama, 323(19), 1891-1892.Ioannidis, J. P., Powe, N. R., & Yancy, C. (2021). Recalibrating the use of race in medical research. JAMA, 325(7), 623-624.Steinecke  A, Terrell  C.  Progress for whose future? the impact of the Flexner Report on medical education for racial and ethnic minority physicians in the United States.  Acad Med. 2010;85(2):236-245.

Production Team

Dr. Gurleen KaurAmit Goyal, MDDaniel Ambinder, MD

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of cardiac sarcoidosis. Show notes created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora!

Cardiac sarcoidosis is a leading cause of morbidity and mortality for patients with sarcoidosis. A high index of suspicion is needed for the diagnosis as it is often recognized late or unrecognized. It is difficult to diagnose given the focal nature of the cardiac involvement limiting the utility of biopsy and the available clinical criteria have limited diagnostic accuracy. Multimodality imaging plays a large role in the diagnosis and management of patients with cardiac sarcoidosis with the different imaging modalities offering complimentary information and functions. 

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Quoatables

“It’s not important for you to love the Soviet Union. It’s important for the Soviet Union to love you back [Stalin regarding the famous dissonant Russian poet Anna Akhmatova]. When we talk about PET, you love PET, but the PET has to love you back, and it has to love you back in a way where you have to know how to approach this test. With, first, some humility about its limitations: 1) inflammation is universal...and 2) the prep is extremely important.”  -- 11:25

“A test without a good preparation is a preparation to fail.” --15:30

“Sarcoidosis is kind of the tuberculosis that we have in medicine—it can present as anything.” --36:40

Pearls

Cardiac Magnetic Resonance Imaging (Cardiac MRI) and/or 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) are complimentary tests in the evaluation of cardiac sarcoidosis. Both tests look for scarring and inflammation. Cardiac MRI is a good initial test due to its high negative predictive value (i.e. absence of LGE makes cardiac sarcoidosis less likely) but not great for following a cardiac sarcoidosis patient’s response to therapy. Cardiac FDG-PET is great to follow a patient's response to therapy especially in patients with intracardiac devices such as a pacemaker.

18-fluorodeoxyglucose (FDG) is a glucose analog and just like glucose, is transported into the cell by transporters. Once in the cell, it is phosphorylated, like glucose is, by hexokinase in preparation for use in glycolysis. Unlike glucose, however, it does not proceed to be metabolized any further in the glycolysis pathway and remains trapped in the cell. In the inflammatory cells within sarcoid granulomas, glycolysis is significantly increased to fuel the large energy requirement. Thus, these inflammatory cells (i.e. macrophages) can take up large amounts of FDG.

When planning to obtain a cardiac FDG-PET for evaluation of cardiac sarcoidosis, patient preparation is key! There are several available dietary protocols to accomplish the goal of switching the patient’s metabolism to be reliant on fatty acids instead of glucose as an energy source. One such protocol used by the discussants in the episode is prolonged fasting (10-12 hours) prior to the study preceded by two meals that are high in fat and proteins and low in carbohydrates—a ketogenic diet. By having the patient eat this diet, we are trying to switch the metabolism because there is no ability or no offer of glucose for the body to use as an energy source! After we have switched the body’s metabolism to purely fat, when we inject the patient with FDG, hopefully most of the myocardium not affected by inflammatory cells within a granuloma will not have any uptake!

Why do we start with resting perfusion images in the imaging portion of the cardiac FDG-PET protocol for cardiac sarcoidosis? Resting perfusion images allow us to identify any perfusion defects at baseline. These images can be compared to the FDG images to see if there is match or mismatch in areas of abnormalities. Resting perfusion images also allow us to assess LV and RV function. Resting perfusion images in conjunction with FDG images can also allow us to monitor the patient’s response to treatment by demonstrating return to normal myocardium from active sarcoid granuloma after treatment or by showing the progression to development of scar.

The hallmark for detecting cardiac sarcoidosis with cardiac MRI is late gadolinium enhancement (LGE) in the mid-wall and subepicardial regions. Gadolinium is an extracellular contrast agent that washes out slowly from areas of inflammation or scar (both processes with result in an expansion of the extracellular space). Because of this it is important to look at the distribution pattern of the LGE (i.e. a subendocardial enhancement in a coronary distribution is more suggestive of scar from a prior myocardial infarction in this area). Some features of LGE that favor the diagnosis of cardiac sarcoidosis include: 1) multifocal involvement and 2) involvement of the basal anteroseptum and inferoseptum with contiguous spread into the right ventricle.

Show Notes

1. What is the typical patient population with cardiac sarcoidosis and how does it present?

Sarcoidosis is a multisystem disorder of unclear etiology characterized by the formation of noncaseating granulomas in multiple organs with an annual incidence of 5 to 40 cases per 100 000 persons in the USA and Europe. It has a 3-fold higher risk in blacks than in whites and it is more common in females. In the USA most disease occurs between ages 25-45, however in Europe and Japan there is a second peak in women older than 70 years old.

Around 5% of patients with pulmonary/systemic sarcoidosis have symptomatic cardiac involvement and autopsy studies have shown that there is cardiac involvement in 25% of patients. More recent advanced cardiac imaging studies in patients with known extracardiac sarcoidosis suggests asymptomatic cardiac involvement may be present in ~40% of patients. It is difficult to detect given its patchy focal distribution in the heart such that cardiac biopsy has a sensitivity of only 20-30% (this yield may improve with image guidance from cardiac MRI or FDG PET or guidance from electroanatomic voltage mapping). 

We may suspect cardiac sarcoidosis in patients presenting with new and unexplained atrioventricular (AV) block, atrial or ventricular arrhythmias, or left ventricular dysfunction—especially in patients with a history of prior non-cardiac sarcoidosis. Palpitations, presyncope, syncope or other nonspecific symptoms may also be the initial presentation.As with our patient in the episode, we should suspect cardiac sarcoidosis and infra-hisian disease in a young previously healthy and active patient who is presenting with evidence of cardiac conduction system disease (i.e. AV block, bundle branch block [BBB], etc.)!

2. Using the patient from the episode as an example (previously healthy presenting with syncope, BBB, frequent non-sustained tachycardia on telemetry monitoring, and intermittent complete heart block, with bilateral hilar fullness on chest x-ray), how should we proceed with evaluation for patients with suspected cardiac sarcoidosis?

To continue our evaluation, we could obtain an echocardiogram to look for wall motion abnormalities and myocardial thinning in the basal areas—findings that can be seen with cardiac sarcoidosis. Even if this is evident, we should still rule out coronary artery disease (CAD) in these patients. In a patient with low risk factors for CAD, we can pursue a coronary computed tomography angiogram (CCTA) and if there is no evidence of obstructive CAD, then we start thinking about an inflammatory process with resultant scar causing the patient’s echocardiography findings. If we have an elderly patient or a patient with significant risk factors for obstructive CAD, then we can obtain a coronary angiogram for evaluation. The bottom line is: common things being common—we don’t want to miss obstructive CAD!Abnormal findings on echocardiography in patients with cardiac sarcoidosis include wall motion abnormalities, diastolic dysfunction, and changes in the left ventricular geometry including: 1) abnormal myocardial wall thickness in a noncoronary distribution (possibly caused by sarcoid granulomas), 2) myocardial wall thinning as a result of a later stage of the same process, 3) left ventricular dilation, and 4) left ventricular systolic dysfunction.Sensitivity, specificity, and negative predictive value of echocardiography for diagnosis of cardiac sarcoidosis are low.There are recent studies that have been published about the value of strain imaging with echocardiography in the diagnosis and assessment of response to therapy of patients with cardiac sarcoidosis, however this is still an evolving area or research.After ruling out obstructive CAD we can proceed to Advanced Cardiac Imaging modalities for further evaluation: Cardiac Magnetic Resonance Imaging (Cardiac MRI) and/or 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET).  These are complimentary tests. Both tests look for scarring and inflammation. Cardiac MRI is a good initial test but not great for following a cardiac sarcoidosis patient’s response to therapy. Cardiac FDG-PET is great to follow a patient's response to therapy especially in patients with intracardiac devices  such as pacemaker or ICD....

CardioNerds (Amit Goyal and Daniel Ambinder), join cardiology fellows from the University of Chicago, (Dr. Mark Belkin, Dr. Ian Hackett, and Dr. Shirlene Obuobi) for an important discussion about case of a woman presenting with implantable cardioverter-defibrillator (ICD) discharges found to be in ventricular tachycardia (VT) storm and work through the differential of ventricular arrhythmias, etiologies of heart failure, and indications for permanent pacemaker and ICD placement. Advanced imaging modalities that aid in the diagnosis of cardiac sarcoidosis, manifestations and management of cardiac sarcoidosis are also discussed. Dr. Nitasha Sarswat and Dr. Amit Patel provide the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Leticia Helms.

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Case Media

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Episode Teaching

Pearls

The etiology of wide-complex tachycardias (WCT) of ventricular origin can be broken down by structurally normal versus structurally abnormal hearts. WCT in structurally normal hearts can be further broken down into idiopathic or primary arrhythmia syndromes. WCT in structurally abnormal hearts can be broken down into ischemic and non-ischemic etiologies.In patients with an unexplained non-ischemic cardiomyopathy, conduction abnormalities and/or ventricular arrhythmias should raise suspicion for cardiac sarcoidosis. Additional manifestations include atrial arrhythmias and  pulmonary hypertension.Accurate diagnosis and treatment of cardiac sarcoidosis often requires multimodality cardiovascular imaging. Check out these terrific videos from Cardiac Imaging Agora: 1) PET for inflammation/sarcoidosis and 2) Echo and CMR for sarcoidosis.While a pathological tissue diagnosis is the gold-standard, endomyocardial biopsy has a low sensitivity, weven when paired with image guidance. Remember to consider extra-cardiac sites for biopsy.Decisions regarding ablation of ventricular arrhythmia or ICD placement should be done individually with careful assessment of active inflammation secondary to cardiac sarcoidosis and possible response to immunosuppressive medications.Management of cardiac sarcoidosis has two basic principles: 1) Treat the underlying process with immunosuppression and 2) Treat the cardiac sequelae: heart failure, conduction abnormalities, ventricular arrhythmias, atrial arrhythmias, and pulmonary hypertension.

Notes

1. The patient in this case was found to be in VT storm. Taking a step back, when we suspect a wide complex tachycardia (WCT) is VT, what are some etiologies we should keep in mind?

Differentiating between a supraventricular vs. ventricular origin of a WCT will be a topic for a future episode! But after you have determined that the origin of WCT is ventricular, considerations for the underlying etiology should include ischemia-related, non-ischemic cardiomyopathy-associated, primary arrhythmia syndromes and idiopathic (in addition to common considerations such as medications and electrolyte abnormalities)Chronic ischemia-related WCT is typically scar-mediated, a result of re-entrant mechanism and more commonly presenting as monomorphic VT. WCT in the setting of acute ischemia is likely a result of combination increased automaticity and re-entry, typically manifesting as polymorphic VT.  In fact, acute ischemia is the most common cause of polymorphic VT, not Torsades de Pointes, and should be our first consideration. Torsades de Pointes specifically occurs due to an early afterdepolarization in a patient with an acquired or congenital prolonged QT interval.Non-ischemic related WCT etiologies in structurally abnormal hearts include (but not limited to) cardiac sarcoidosis, myocarditis (specifically giant-cell myocarditis), hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left dominant arrhythmogenic cardiomyopathy and Chagas disease. Especially in patients with dilated CM, if your initial evaluation does not reveal an etiology, then genetic testing should be considered to identify genetic sources of arrhythmogenic cardiomyopathies, such as laminin and desmoplakin mutations (See Episode 56: CNCR with Northwestern University!)Primary arrhythmia syndromes include, but are not limited to, Brugada, Long QT, Short QT, and catecholaminergic polymorphic VT (CPVT). Idiopathic WCT includes outflow tract, fascicular, or papillary muscle ventricular tachycardias (VT).

2. What is the underlying pathophysiology for the cardiac manifestations of sarcoidosis?

Typically, the clinical manifestations of cardiac sarcoidosis depend on the extent and location of the inflammatory process and subsequent fibrosis. Granulomas can be found anywhere in the heart, though more commonly involve the interventricular septum and left ventricle.The most common presentations include conduction abnormalities (e.g., atrioventricular block, right bundle branch block), atrial and ventricular arrhythmias, and less commonly clinical heart failure. Of note, AV blocks and ventricular arrhythmia increase the risk of sudden cardiac death, which may be the first manifestation of cardiac sarcoid.Furthermore, RV involvement is common in cardiac sarcoid – whether it be from the hemodynamic consequences of extensive LV involvement, pulmonary hypertension (pre- and post-capillary mechanisms) or direct RV involvement. However, isolated RV involvement is rare.Sarcoidosis-associated pulmonary hypertension may be present in 5-20% of patients with sarcoidosis and is multifactorial with FIVE major etiologic categories: