Episodes Archives - Cardionerds

In this special CardioOB series patient perspective episode, CardioNerds (Amit Goyal and Daniel Ambinder), join three incredible WomenHeart Champions, Ms. Porothea Dennis, Ms. Brandie Taylor, and Ms. Ellen Robin in the presence of two legendary leaders in cardiovascular medicine,  Dr. Nanette Wenger and Dr. Sharonne Hayes. In addition to this episode being featured on our Cardio-Obstetrics topic page, you can also find this episode in our Patient and Family Perspective collection which features several moving and meaningful patient and family stories that remind us of why we do what we do. Special message by Ms. Celina Gorre, CEO of WomenHeart. Audio editing by CardioNerds Academy Intern, Dr. Leticia Helms.

The CardioNerds Cardio-Obstetrics series is a comprehensive series led by series co-chairs Dr. Natalie Stokes CardioNerds ambassador from UPMC and Dr. Sonia Shah CardioNerds ambassador from UTSW, and produced in collaboration with WomenHeart.

There is no CME for this episode. Relevant disclosures: None.

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Why Cardio-Obstetrics❓ Because it’s important, and relevant to anyone taking care of women who are, may become, or have been pregnant as cardiovascular disease is the #1 cause of pregnancy-related death. 

In order to raise awareness we’ve put together an fun, sometimes sobering, but comprehensive curriculum, so get ready, because this CardioNerds Cardio-Obstetrics cruise will dock at several ports along the way: ✔normal pregnancy physiology, ✔hypertensive disorders, ✔arrhythmia, ✔valvular heart disease, ✔anticoagulation, ✔pulmonary hypertension, ✔congestive heart failure, ✔aortopathies, ✔coronary artery disease, ✔critical care, ✔4th trimester, ✔Racial disparities in care, ✔interventional considerations, ✔patient perspectives including from womenheart champions, and more!

• Natalie Stokes, MD
• Sonia Shah, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

Join CardioNerds for a great discussion about key ACC 2021 Prevention highlights featuring the ADAPTABLE and STRENGTH trials. This episode is produced in collaboration with the American College of Cardiology Prevention of Cardiovascular Disease Council with mentorship from the Council’s Chair Dr. Eugene Yang (University of Washington Medical Center) who provides a message at the end of the episode.  

First, Dr. Amit Goyal and Council Representative Dr. Mahmoud Al Rifai (FIT, Baylor College of Medicine) discuss the implications of the ADAPTABLE Trial with Dr. Gina Lundberg (Emory University School of Medicine).  

Then Dr. Tommy Das (FIT, Cleveland Clinic), Dr. Rick Ferraro (FIT, Johns Hopkins) and Council Representative Dr. Anum Saeed (FIT, University of Pittsburgh Medical Center) discuss the results of the STRENGTH trial’s secondary analysis with Dr. Steven Nissen (Cleveland Clinic).  

Disclosures: Dr Nissen reported grants from AstraZeneca during the conduct of the STRENGTH trial

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ADAPTABLE Trial 

The ADAPTABLE trial is a randomized open label pragmatic trial comparing two doses of aspirin (325 mg vs. 81 mg) for the secondary prevention of cardiovascular disease. The trial employed a range of innovative and low-cost methods to simplify the identification, recruitment, and follow-up of patients. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety outcome was hospitalization for major bleeding. 

A total of 15,076 patients were followed for a median of 26.2 months. The primary effectiveness and safety outcomes were not significantly different between the two groups. Together with Dr. Lundberg we discuss design and methodological issues related to the trial and applicability to clinical practice.  

• ASA 81 mg is as effective as ASA 325 mg for reducing cardiovascular events 
• ASA 325 mg does not cause more bleeding episodes than ASA 81 mg 
• ASA dosing should be based on a clinician-patient risk discussion incorporating patients’ risk profile and their values and preferences  
• Future trials should ensure adequate representation of women and race/ethnic minorities  

The results of the present trial suggest that either dose of ASA (81 mg or 325 mg) would be adequate to lower patients’ risk of death or atherosclerotic cardiovascular events with similar risk of bleeding. ASA dosing should be based on patient values and preferences and clinician judgement as the effectiveness and safety profile of these two regiments appears to be equivalent on the basis of the present trial.  

STRENGTH Trial, Secondary Analysis 

Whether omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk has been long debated. Data have largely remained inconclusive with several previous trials, particularly the VITAL and ASCEND, showing no significant cardiovascular benefit DHA and EPA supplementation. However, the REDUCE-IT and the JELIS trials showed cardiovascular benefit with higher dose of purified EPA compared to placebo.  Meanwhile, the STRENGTH trial did not show any difference in CVD outcomes in treatment groups using a combined EPA/DHA formulation. 

In this episode, we discuss a secondary anaylsis from the STRENGTH trial entitled “Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk” presented at the ACC 2021 addressing the effects of carboxylic acid formulation of EPA/DHA (omega-3 CA) compared with placebo among patients with dyslipidemia and high cardiovascular risk.  

This analysis showed that there was no added clinical benefit or harm in those who achieved the highest tertiles of EPA and DHA. 

• “It is very important to use a neutral comparator as a placebo and this is what we aimed to do in the STRENGTH trial by using corn oil as the placebo against EPA/DHA… you can only optimally interpret a clinical trial in the context of a neutral placebo.”  

• The STRENGTH trial used carboxylic acid derivative which is better absorbed than other ester formulations used in other studies and its absorption is independent of food. 

• The EPA concentration in the blood reached adequate levels (even up to 268% in the pooled analysis) in this study however, there was only a ~39% increase in DHA even though a formulation of both EPA and DHA was used. Reasons for this remain to be uncovered.  

• Three most recent trials including REDUCE-IT, STRENGTH and OMEMI trial have all consistently showed an increase in atrial fibrillation with omega-3 FA use. The incidence is small but not trivial. Mechanistically, we do not know the reason for this.   

• Opportunity to do further studies studying the effects of Omega-3FA on atherosclerotic disease itself and its progression or reduction remains wide open.  

Dr. Yang is medical director of the UW Medicine Eastside Specialty Center and a UW professor of medicine. He has particular expertise in the diagnosis and treatment of coronary artery disease, valvular heart disease, peripheral vascular disease, congestive heart failure, cardiac arrhythmias, hypertension and lipid disorders. He is especially interested in the primary and secondary prevention of heart disease through aggressive risk-factor modification and lifestyle change. He also conducts research on new cholesterol-lowering therapies and appropriate treatment options for patients with coronary artery disease. 

Dr. Yang received his bachelor’s and master’s degrees from Stanford University and his medical degree from the University of Pennsylvania School of Medicine. He completed his internal medicine residency and fellowships in cardiovascular disease and advanced cardiac imaging at Stanford University School of Medicine. Prior to joining the faculty at UW Medicine, he was a clinical instructor and physician-scientist at Stanford. 

Dr. Yang has been on the faculty at UW Medicine since 2007 and is actively involved with the teaching of medical students, residents and fellows. He is a fellow of the American College of Cardiology and is board certified in internal medicine and cardiovascular disease. Dr. Yang’s personal interests include food, wine, golf, travel, and watching soccer.

Gina Price Lundberg MD FACC FAHA is an Associate Professor of Medicine at Emory University School of Medicine and has served as the Clinical Director of the Emory Women’s Heart Center since it was founded in 2013. She is a Preventive Cardiologist and specializes in heart disease in women, lipid abnormalities and cardiovascular risk reduction. She founded the first women’s heart prevention program in the state of Georgia in 1998. Dr Lundberg’s service at Emory University includes improving outcomes for women with cardiovascular disease but also improving gender equity for women in cardiology and encouraging more women to choose cardiology for their careers. She attended the Medical College of Georgia at Augusta University and trained in Internal Medicine at Atlanta Medical Center. Her cardiology fellowship was at Rush University in Chicago. She is active with the ACC, AHA, and NLA. She is the Chair-elect for the ACC Women in Cardiology Leadership Council and is the co-chair for the WIC Communications and Social Media Committee. She is the Co-chair for the NLA Social Media and Communications committee and the co-Chair for NLA DE&I Committee. She serves on the AHA Clinical Cardiology Communications and Social Media committee and the AHA Familial Hypercholesterolemia and Hyperlipidemia working group. And she serves as the Social Media Supervisor for JACC Case Reports.

Steven Nissen, MD, is Chief Academic Officer, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute, and holds the Lewis and Patricia Dickey Chair in Cardiovascular Medicine. Dr. Nissen has more than 35 years of experience as a physician. He is world-renowned for his work as a cardiologist, patient advocate and researcher. Equally as significant is his pioneering work in IVUS technology and its use in patients with atherosclerosis. Dr. Nissen has written more than 400 journal articles and 60 book chapters, including many published in the New England Journal of Medicine and the Journal of the American Medical Association. In recent years, he has also written on the subject of drug safety and was the author of manuscripts highlighting concerns about medications such as Vioxx™, Avandia™, and muraglitazar. He is heavily involved with the American College of Cardiology (ACC), serving as President from March 2006 to March 2007, a member of the ACC Executive Committee from 2004 to 2008, and spending 10 years as a member of the organization’s Board of Trustees. In addition, Dr. Nissen has served several terms on the Program Committee for the ACC Annual Scientific Sessions. In his leisure time, Dr. Nissen likes to bicycle whenever possible. He is also an advanced amateur photographer.

Dr. Mahmoud Al Rifai earned his medical degree from American University of Beirut
and M.P.H. from Johns Hopkins Bloomberg School of Public Health. He completed his internal medicine residency training at University of Kansas – Wichita where he also completed a chief residency year. His career interests include academic cardiology, imaging, risk prediction, cardiovascular disease prevention and his hobbies include tennis, healthy lifestyle, reading, and coffee making.

Dr. Anum Saeed is a Clinical Instructor/Postdoctoral Associate at the University of Pittsburgh and cardiologist at UPMC. She completed her general cardiology fellowship from UPMC in June 2021 and an Atherosclerosis & Lipidology fellowship from Baylor College of Medicine in 2018. Her research focuses on studying lipids and atherosclerosis in cardiovascular disease and dementia prevention.

Jones WS, Mulder H, Wruck LM, et al., on behalf of the ADAPTABLE Team. Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease. N Engl J Med 2021; 384:1981-1990

Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020;324(22):2268–2280. doi:10.1001/jama.2020.22258

• Amit Goyal, MD
• Daniel Ambinder, MD

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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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.

1. Douglas, P. S., Williams, K. A., & Walsh, M. N. (2017). Diversity matters.
2. 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/facts
3. Yancy, C. W. (2020). COVID-19 and African Americans. Jama, 323(19), 1891-1892.
4. Ioannidis, J. P., Powe, N. R., & Yancy, C. (2021). Recalibrating the use of race in medical research. JAMA, 325(7), 623-624.
5. 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.

• Dr. Gurleen Kaur
• Amit Goyal, MD
• Daniel 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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“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

1. 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.

1. 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.

1. 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!

1. 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.

1. 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.

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. These patients can also have a cardiac MRI done but the diagnostic yield becomes more challenging. Let’s discuss the details and characteristic findings of Cardiac FDG-PET and Cardiac MRI in the next sections, and then circle back and continue our discussion of some comparisons between the two modalities in the evaluation and management of cardiac sarcoidosis.

3. Why is patient preparation prior to a cardiac FDG-PET study for evaluation of cardiac sarcoidosis so important? How do we utilize cardiac FDG-PET in the diagnosis of cardiac sarcoidosis?

• There are three main components to the cardiac FDG-PET study for evaluation of cardiac sarcoidosis: 1) Patient preparation with high-fat, high-protein, low-carbohydrate meals followed by prolonged fasting for 10-12 hours prior to the study in an effort to switch the body’s metabolism to using primarily fatty acids as a source of energy, 2) A resting perfusion imaging component using either Rubidium-82 or N-13 Ammonia, and finally 3) the FDG-imaging component. After obtaining resting perfusion images, the patient may or may not be given intravenous heparin (for lipolysis—discussed further below) and then an intravenous injection of the FDG. They are given around a 90 minute period to allow  for FDG uptake during which they are asked to rest quietly (to minimize skeletal muscle uptake of FDG!). After this, images of the heart looking for FDG uptake are obtained. Following this, whole-body imaging from the base of the skull to the mid-thigh is done to help identify extracardiac sites of sarcoidosis.
• What is the philosophy behind the required strict patient preparation prior to a cardiac FDG-PET study for evaluation of cardiac sarcoidosis? 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.
  • The heart primarily functions with fatty acid uptake, however, it does have some glucose uptake as well—especially those areas that are ischemic or hibernating. We want FDG to only be taken up by inflammatory cells within a potential granuloma and minimize the uptake of FDG by other myocardial cells. Preparation is key!
  • There are several available dietary protocols to accomplish this goal. 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!
    • For patient’s receiving intravenous infusions during a hospital admission, it is important to avoid including dextrose in the formulations!
  • Along with the above diet, we also don’t want the patient engaging in vigorous physical activity on the day of or day prior to the test as there will then be musculoskeletal uptake of FDG rather than myocardial uptake. We try to avoid simultaneously doing stress imaging during the same encounter as sarcoid imaging because we don’t want to induce ischemia that could potentially induce FDG uptake by the ischemic myocardium. Exercise or pharmacologic stress can induce myocardial ischemia which shifts the metabolism from fatty acids to glucose. Despite this change happening in minutes after the onset of ischemia, it can persist for a long time, so that if you inject FDG after this, that area of ischemic myocardium will light up. This is known as “ischemic memory!”
    • If a simultaneous stress testing evaluation is needed in addition to evaluation for cardiac sarcoidosis, then you can do the rest perfusion imaging and FDG portion on Day 1 and the stress perfusion imaging portion on Day 2.
  • As mentioned above, some centers use intravenous heparin prior to the FDG imaging portion with the thought being that heparin induces lipolysis and can increase the offer of fatty acids to the myocardium (every effort to shift the metabolism!)
  • Frequently on cardiac FDG-PET imaging, patients have failed to suppress the myocardium uptake of glucose due to suboptimal compliance. A study by Dr. Erika Hutt (a discussant on the episode!) and Dr. Paul Cremer is being done with the use of a ketone shake for breakfast and lunch on the day before the study followed by fasting after lunch until the study the following day and is finding that in patients who failed to suppress the myocardium with a standard diet, these patients were able to suppress the myocardium with ketone shake.
    • Additionally, it can be challenging for vegans and vegetarians to follow the high protein component of the diet given the lack of meat in their normal diet. For these patients it is more difficult to adhere to the diet (typically some formulation of tofu or oil can be recommended), but ketone shake may also be helpful in this situation.
• 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. This is particularly important because despite the patient’s and our best efforts with the patient preparation, we may not be successful in suppressing the myocardium. In these situations we may FDG-uptake in normal myocardium. Resting perfusion imaging can help clarify this situation—if there is a matching perfusion defect, then this likely represents an area of inflammation. If there is no matching perfusion defect, this FDG avid area may represent an area of inflammation in cardiac sarcoidosis in the early stages of the disease when scar has not yet developed or it may represent FDG uptake by normal myocardium due to our failure to suppress the myocardium. 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.
  • When analyzing the cardiac FDG-PET cardiac sarcoidosis study, there are a few potential scenarios in addition to the scenario mentioned above (normal resting perfusion and FDG uptake) :
    • Normal resting perfusion and no FDG uptake
      • Normal Study
    • Resting perfusion defect and focal FDG uptake in the same area
      • Possible early stage of cardiac sarcoidosis with the perfusion defects either representative of: 1) compression of the microvasculature by inflammation or 2) scar related to fibrosis
      • This can also be seen in viability studies which suggest that there is an area of viable myocardium in a myocardial region with scar secondary to coronary artery disease. However, the patient preparation for a viability study with FDG PET and a cardiac sarcoidosis study with FDG PET are very different, so this possibility is less likely. Importantly, we should still be mindful of this possibility and the possibility of obstructive coronary artery disease.
    • Resting perfusion defect and no FDG uptake
      • Representative of scare without any active  inflammation. Notably, this does not rule out cardiac sarcoidosis. This pattern can be seen in later stages of the disease during which a larger burden of scar has developed compared to the amount of living cells, and thus, there happens to be no active inflammation (macrophage uptake of glucose results in areas of FDG uptake).
• FDG-PET has both diagnostic and prognostic uses in cardiac sarcoidosis. A prior meta-analysis by Youssef et al. demonstrated a sensitivity and specificity of FDG-PET in identifying cardiac sarcoidosis of 89% and 78% respectively (the lower specificity may have been impacted by the low sensitivity of the available diagnostic criteria which are used as gold standards for reference in these studies). An abnormal FDG-PET with myocardial perfusion defect and focal inflammation had a 4x increased risk of ventricular tachycardia or death irrespective of JMHW criteria and left ventricular ejection fraction. Among patients with active inflammation, those with RV involvement had the highest event rates.
• Whole-body imaging is particularly important when there is a high clinical suspicion of cardiac sarcoidosis. In these cases, if we see extra-cardiac involvement (i.e. Hilar lymphadenopathy that lights up or mesenteric lymphadenopathy that lights up) and we have evidence of conduction system abnormalities, then we know we likely have cardiac involvement even if we don’t see it on images. These extra-cardiac areas of FDG-uptake can also be areas of the body more amenable to biopsy than the heart. Finally, whole-body imaging can help with assessing the need and/or benefit of immunosuppressive therapy.

4.  What are the characteristic findings of cardiac sarcoidosis on cardiac MRI?

• In addition to morphological changes of the ventricle as seen with echocardiography (described above), 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). Even in non-infarct distributions, however, LGE is nonspecific and can be seen in myocarditis or idiopathic cardiomyopathy.
    • 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.
  • Increased T2-weighted signal (a marker of increased water content which can be seen in areas of inflammation) can also suggest inflammation secondary to cardiac sarcoidosis.
  • A prior study by Smedema et al. described a cohort of patients with biopsy proven pulmonary sarcoidosis and evaluated the diagnostic accuracy of cardiac MRI for diagnosing cardiac sarcoidosis in the patients within this cohort who met Japanese Ministry of Health and Welfare (JMHW) diagnostic criteria. The study suggested that the sensitivity and specificity of cardiac MRI for diagnosing cardiac sarcoidosis is 100% and 78% respectively (the lower specificity, as for FDG-PET, may be attributed to the low sensitivity of the JMHW criteria).
  • Just as with FDG-PET, Cardiac MRI also has prognostic value in regards to patients with cardiac sarcoidosis. A study by Greulich et al. showed that in patients with systemic sarcoidosis, LGE had a hazard ratio for death or aborted sudden cardiac death of 31.6. 

5. How should we use cardiac MRI and cardiac FDG-PET in the evaluation of suspected cardiac sarcoidosis?

• In studies comparing cardiac FDG-PET and cardiac MRI in the diagnosis of cardiac sarcoidosis, there are certain situations where FDG-PET has been observed  to be a more sensitive test: 1) patients with new-onset AV block, 2) patients that are more likely to recover from AV block after steroid therapy, and 3) identification of inflammation in cardiac sarcoidosis (as compared to T2-weighted imaging with cardiac MRI). However, cardiac MRI may be more sensitive that FDG-PET for patients who are already on steroid therapy in the diagnosis of cardiac sarcoidosis. In general, FDG-PET and Cardiac MRI provide complimentary information which can help bolster clinical decision making for a disease that is difficult to diagnose, help risk stratify patients for immunosuppressive therapies and ICD placement purposes, and help monitoring for treatment response.
• Because of the high negative predictive value of cardiac MRI for diagnosis of cardiac sarcoidosis, a proposed strategy by Blankstein et al. for patients with suspected cardiac sarcoidosis it to first obtain cardiac MRI as long as there are no contraindications to the study. If this is negative (i.e. if there is absence of LGE), FDG PET can be considered if high clinical suspicion remains. If the cardiac MRI is positive or inconclusive, FDG PET should be obtained for complimentary information for diagnosis, risk stratification, and monitoring response to therapy (data is emerging on risk stratification for sudden cardiac death benefits of FDG-PET however as of the writing of the HRS recommendations in 2014, the writing group felt there was insufficient data to include a formal recommendation on this in their Expert Consensus Statement).
• Osborne et al. showed that a decrease in intensity (assessed by standardized uptake value max [SUVmax]) or extent (volume of inflammation above a prespecified SUV threshold—usually 2.7 g/mL) of inflammation on cardiac FDG-PET was associated with improvement in left ventricular ejection fraction. Thus, this can be used to monitor treatment efficacy and can help with the decision of timing of tapering of steroid therapy and with the decision of whether a different immunosuppressive regimen is needed (if an inadequate response is observed).
• It is also important to consider the expertise and familiarity with different imaging modalities available at the institutions when deciding between imaging modalities.

6. What diagnostic criteria do we have to establish a probable diagnosis of cardiac sarcoidosis?

• The Japanese Ministry of Health and Welfare (JMHW) criteria was used originally for research purposes and then incorporated into clinical practice. It was created in 1993 and modified in 2007 with the addition of some advanced imaging diagnostic criteria. Now, more commonly, the Heart Rhythm Society (HRS) criteria which was more recently introduced and based on more contemporary evidence is being used by most practitioners. Similar to the JMHW criteria, the HRS criteria includes two pathways for the diagnosis of cardiac sarcoidosis: 1) a histological diagnosis, and 2) a clinical diagnosis
  • For histological diagnosis, cardiac sarcoidosis “is diagnosed in the presence of non-caseating granuloma on histological examination of myocardial tissue with no alternative cause identified (including negative organismal stains if applicable).”
  • For clinical diagnosis, information from invasive and non-invasive studies are used. You need to have extracardiac histological diagnosis, no other explanation for the patient’s clinical presentation, and one or more of the following:
    • Cardiomyopathy or heart block that response to steroids or immunosuppressants
    • Unexplained reduction in the LVEF <40%
    • Unexplained high-degree AV block
    • Unexplained sustained ventricular tachycardia
    • Imaging findings suggestive of sarcoid (Patchy uptake of FDG on dedicated Cardiac PET in a pattern consistent with cardiac sarcoidosis or late gadolinium enhancement on Cardiac MRI in a pattern consistent with cardiac sarcoidosis)
    • Positive gallium uptake (in a pattern consistent with cardiac sarcoidosis)

7. Is there are any role for screening for cardiac sarcoidosis?

• The Heart Rhythm Society (HRS) has proposed an Expert Consensus recommendation for screening for cardiac sarcoidosis suggesting that all patients with biopsy-proven extracardiac sarcoidosis have an ECG done to screen for conduction system disease and asked about suggestive symptoms such as palpitations, presyncope, and syncope.  Echocardiography may be helpful (however, as discussed above, echocardiography is insensitive and a normal LVEF and normal wall motion does not exclude cardiac sarcoidosis). 
• In patients with biopsy-proven or clinically diagnosed extracardiac sarcoidosis who have signs or symptoms or possible cardiac involvement based on ECG, echocardiography, or symptoms further screening with cardiac MRI or FDG-PET may be useful.
• Screening with advanced cardiac imaging and high resolution CT chest may also be helpful in patients with no previous history of sarcoidosis but who have unexplained Mobitz II, third-degree AV block (sustained monomorphic ventricular tachycardia was also felt to be reasonable by a majority of the writing group for the HRS recommendations, however the vote did not reach a predefined threshold to become a formal recommendation).
  • If advanced imaging and high resolution CT chest are suggestive of cardiac sarcoidosis, extra-cardiac biopsy if feasible or guided endomyocardial biopsy can be pursued to confirm the diagnosis.
• Finally, there is noted overlap in the presentation of arrhythmogenic right ventricular cardiomyopathy and cardiac sarcoidosis. The literature is still emerging on the topic and thus, there are no formal guidelines for screening yet.

Wael Jaber, MD, is a staff cardiologist in the Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, at the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. Dr. Jaber specializes in cardiac imaging (both nuclear cardiology and echocardiography) and valvular heart disease. Dr. Jaber attended college at the American University in Beirut, graduating with a Bachelor of Science in biology. He then went on at the American University to receive his medical degree while making the Dean’s honor list. He completed his residency in internal medicine at the St. Luke’s-Roosevelt Hospital Center at Columbia University College of Physicians and Surgeons, where he also completed fellowships in cardiovascular medicine and nuclear cardiology. Dr. Jaber is currently is the Medical Director of the Nuclear Lab and of the Cardiovascular Imaging Core Laboratory in C5Research. He is fluent in English, French and Arabic. He is the author of Nuclear Cardiology review: A Self-Assessment Tool and cofounder of Cardiac Imaging Agora.

Dr. Aldo L Schenone is one of the current Chief Non-Invasive Cardiovascular Imaging Fellows at the Brigham and Women’s Hospital. He completed medical school at the University of Carabobo in Valencia, Venezuela, and then completed both his Internal Medicine residency and Cardiology fellowship at the Cleveland Clinic where he also served as a Chief Internal Medicine Resident.

Dr. Erika Hutt @erikahuttce is a cardiology fellow at the Cleveland Clinic. Erika was born and raised in Costa Rica, where she received her MD degree at Universidad de Costa Rica. She then decided to pursue further medical training in the United States, with the goal of becoming a cardiologist. She completed her residency training at Cleveland Clinic and went on to fellowship at the same institution. Her passions include infiltrative heart disease, atrial fibrillation, valvular heart disease and echocardiography among many. She is looking forward to a career in advanced cardiovascular imaging.

1. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm. Jul 2014;11(7):1305-23. doi:10.1016/j.hrthm.2014.03.043

2. Blankstein R, Waller AH. Evaluation of Known or Suspected Cardiac Sarcoidosis. Circ Cardiovasc Imaging. Mar 2016;9(3):e000867. doi:10.1161/CIRCIMAGING.113.000867

3. Freeman AM, Curran-Everett D, Weinberger HD, et al. Predictors of cardiac sarcoidosis using commonly available cardiac studies. Am J Cardiol. Jul 2013;112(2):280-5. doi:10.1016/j.amjcard.2013.03.027

4. Greulich S, Deluigi CC, Gloekler S, et al. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging. Apr 2013;6(4):501-11. doi:10.1016/j.jcmg.2012.10.021

5. Iannuzzi MC, Fontana JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. Jan 2011;305(4):391-9. doi:10.1001/jama.2011.10

6. Skali H, Schulman AR, Dorbala S. (18)F-FDG PET/CT for the assessment of myocardial sarcoidosis. Curr Cardiol Rep. May 2013;15(5):352. doi:10.1007/s11886-013-0352-8

7. Smedema JP, Snoep G, van Kroonenburgh MP, et al. Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol. May 2005;45(10):1683-90. doi:10.1016/j.jacc.2005.01.047

8. Youssef G, Leung E, Mylonas I, et al. The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience. J Nucl Med. Feb 2012;53(2):241-8. doi:10.2967/jnumed.111.090662

• Wael Jaber, MD

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.

Claim free CME just for enjoying this episode! Disclosures: Dr. Amit Patel disclosed ownership of small stocks in GE Healthcare Bio-Sciences.

Jump to: Case media – Case schematic & teaching – References

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1. 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.
   
2. 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.
   
3. 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.
   
4. 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.
   
5. 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.
   
6. 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.

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:
  1. Cardiac: Group 2 (post-capillary) PH from elevated left-sided filling pressures related to heart failure.
  2. Parenchymal: Group 3 PH related to pulmonary parenchymal fibrosis.
  3. Vascular: vasculitis, arteritis, pulmonary embolism, pulmonary venoocclusive disease
  4. Anatomic: adenopathy compressing arteries, vascular distortion from pulmonary fibrosis, fibrosing mediastinitis
  5. Comorbidities: portopulmonary hypertension (if there is hepatic involvement), anemia, OSA.

3. How do we utilize multi-modality imaging in the diagnosis of cardiac sarcoidosis?

• Multi-modality imaging aids in the diagnosis of cardiac sarcoidosis in two primary ways: (1) evaluating the extent and pattern of myocardial scar/fibrosis and (2) assessing for active inflammation.
• Cardiac magnetic resonance imaging (CMR) is utilized to delineate the pattern of scar if present. As discussed in EP #33, CMR is a powerful tool in the evaluation of cardiomyopathy, allowing quantification of RV/LV size, mass, global/regional function, and identification of myocardial scar by late gadolinium enhancement (LGE). Characteristic scar patterns of cardiac sarcoid include patchy, multifocal LGE typically in the mid-myocardium and sub-epicardium. While a positive CMR scan in the setting of biopsy-proven extracardiac sarcoid is indicative of probable cardiac sarcoid, a negative CMR scan does not exclude subclinical disease.
• PET/CT is also used for the evaluation of cardiac sarcoid, typically to identify the extent of active inflammation, guide immunosuppression therapy and/or if CMR is not available. 18-fluorodeoxyglucose (FDG)-PET/CT requires proper dietary preparation. Macrophages present in inflamed tissues will avidly take up 18F-FDG. But to avoid a false positive we need to suppress physiologic myocardial uptake of glucose to identify only pathologic WBC uptake. One way to suppress physiologic 18F-FDG is to give patients a high fat, ultra-low carb diet (instead of a prolonged fasting state alone), so myocytes preferentially rely on free fatty acids for fuel. PET imaging should be accompanied by an evaluation of myocardial perfusion, similar to the resting portion of a nuclear stress test, to evaluate for defects corresponding to areas of inflammation.
• Note, if 18F-FDG-PET scan reveals diffuse FDG uptake with no perfusion defect this can commonly indicate a false positive result from inadequate suppression of physiologic FDG uptake, as extensively inflamed myocardial should also lead to decreased perfusion in the involved region. See our upcoming Nuclear and Multi-Modality Imaging Series for more on imaging in Cardiac Sarcoid!

4. What is the role of endomyocardial biopsy in the diagnosis of cardiac sarcoidosis?

• Endomyocardial biopsy (EMB) historically has only a 25% success rate due to the patchiness of cardiac sarcoidosis. There are improved chances of success if EMB is done via an image-guided or electro-anatomical guided method, but sensitivity remains insufficient to rule out cardiac sarcoidosis even with guided biopsies.
• Importantly, to confirm the diagnosis of cardiac sarcoidosis, per the 2014 Heart Rhythm Society (HRS) Expert Consensus Recommendation, pathological tissue of non-caseating granulomas is needed. This can either be directly from the myocardium, via EMB, or from an extra-cardiac source when  paired with at least one cardiac manifestation. Common places to biopsy include mediastinal lymph nodes via bronchoscopy or lymph nodes near the skin surface. Extra-cardiac sites can be identified on whole-body PET scans by FDG-uptake, as described above.

5. What is the role of VT ablation and ICD placement in cardiac sarcoid?

Ventricular arrhythmia ablation is considered on an individual patient basis in cardiac sarcoidosis. Patients should be assessed for active inflammation, and if present, they should typically first be treated with immunosuppression as this may suppress the arrhythmias without ablation. Antiarrhythmic medications may be added to help prevent additional VT episodes. If ventricular arrhythmias persist despite adequate immunosuppressive and anti-arrhythmic treatment, then ablation may be considered.

According to the HRS guidelines, ICD implantation in cardiac sarcoid is given a Class I indication if the patient has sustained VT (including prior cardiac arrest) and/or LVEF <35% despite optimizing immunosuppression. EP study, CMR and/or PET can be used to guide ICD implantation on an individual basis in patients not meeting a Class I indication. ICD implantation is not recommended (Class III) in patients with no history of syncope, normal LVEF/RVEF, no LGE on CMR, negative EP study, no indication for permanent pacing, incessant VT, or severe NYHA Class IV heart failure.

6. What are common immunosuppressive regimens in cardiac sarcoid?

• Immunosuppression regimens vary institution to institution, and often physician to physician. Prednisone is the most common first line agent. It has been shown to improve atrioventricular conduction, mild-moderate left ventricular dysfunction, and burden of ventricular arrhythmias. Most often patients are started on higher doses of prednisone, and then subsequently weaned off with the goal of fully stopping, or reducing to as low a dose as possible, so as to avoid the chronic side effects of prednisone. Common steroid-sparing agent include methotrexate, azathioprine, and mycophenolate. In refractory cases, biologic therapies such as infliximab or rituximab can be used.
• Repeat cardiac PET scans can be done to assess for improvement in inflammation, often two to three months after starting treatment. The timing and frequency of this repeat imaging is not well delineated and may vary between institutions and physicians. Finally, aside from immunosuppression, there are limited data on use of standard heart failure guideline-directed medical therapy (GDMT) in these patients. Overall, it is recommended that patients with reduced ejection fraction (EF) are put on the same GDMT as the standard patient with a reduced EF, as they may have beneficial effects in regard to EF improvement and heart failure-related outcomes.

1. Birnie DH, Sauer WH, Bogun F et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014;11:1305-23.
2. Birnie DH, Nery PB, Ha AC, Beanlands RS. Cardiac Sarcoidosis. J Am Coll Cardiol 2016;68:411-21.
3. Trivieri MG, Spagnolo P, Birnie D,  et al. Challenges in Cardiac and Pulmonary Sarcoidosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Oct 20;76(16):1878-1901. doi: 10.1016/j.jacc.2020.08.042.
4. Shlobin OA, Baughman RP. Sarcoidosis-Associated Pulmonary Hypertension. Semin Respir Crit Care Med. 2017. doi:10.1055/s-0037-1603767

• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds Academy Chief Fellows Dr. Rick Ferraro (FIT, Johns Hopkins) and Dr. Tommy Das (FIT, Cleveland Clinic) join Academy fellow Dr. Jessie Holtzman (soon, chief resident at UCSF internal medicine residency) to learn all about LDL physiology and function from Dr. Peter Toth!

Low-density lipoprotein cholesterol (LDL-C) has been well established as a risk factor for atherosclerotic cardiovascular disease with an ever growing armamentarium of medications to lower LDL-C plasma levels. Yet, LDL-C also plays a number of key physiologic roles across mammalian species, such as cell membrane formation, bile acid synthesis, and steroid hormone production. In this episode, we discuss the definitions of high, normal, low, and ultra-low LDL-C, what functional assays are used to measure LDL-C, and what is considered the safe lower-limit of LDL-C, if there is one at all. Drawing upon experience from rare genetic conditions including abetalipoproteinemia and loss-of-function variants of the PCSK9 gene, we glean pearls that clarify  the risks and benefits of low LDL-C.

Relevant disclosure: Dr. Toth has served as a consultant to Amarin, Amgen, Kowa, Resverlogix, and Theravance; and has served on the Speakers Bureau for Amarin, Amgen, Esperion, and Novo Nordisk.

Pearls • Quotables • Notes • References • Guest Profiles • Production Team

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1. Lipoproteins are processed via two major pathways in mammals: 1) exogenous fat metabolism that digests ingested lipids and 2) endogenous fat metabolism that synthesizes lipids in the liver and small intestine. High density lipoprotein (HDL)-mediated reverse transport also brings lipids from the periphery back to the liver.

2. LDL-C comprises ~70% of plasma cholesterol due to its long half-life of 2-3 days. It is one of 5 major lipid particles in plasma including chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), LDL, and HDL. The liver degrades 40-60% of LDL, while no other tissues in the body make up more than 10% of LDL. LDL-C is energy-poor and cholesterol rich, such that peripheral tissues may not utilize these particles as a fuel source.

3. Preserved functions of LDL-C across mammalian species include cell membrane formation, bile acid synthesis, and steroid hormone production. In other mammalian species, LDL-C levels are found in the 35-50 mg/dL range (Way lower than found in the general human population, and likely more representative of baseline human physiology!).

4. Large, randomized control trials do not consistently demonstrate major adverse effects associated with lower serum LDL-C levels, including risks of cognitive decline, hemorrhagic stroke, reduced bone density, or impaired immune function.

5. Initiation of, and education on LDL-lowering therapy remains insufficient, both in terms of long-term adherence to therapy and achieving current guideline directed goals of LDL-C <70mg/dL (And even lower in specific scenarios, such as repeat cardiovascular events).

“It’s pretty clear that this is an area where you can make a profound difference in the lives of people. It’s very clear from the clinical trials that when we initiate therapies, whether it’s lifestyle, through a statin, or an antihypertensive, you impact not only the quality of life, but the quantity of life. You make life better, you make life freer of disability, and you forestall death.”

“The bottom line is that LDL is spent garbage liquid and it is tantamount that the body be well-equipped to remove this LDL from the central circulation, because I will argue today that it is the single most important toxin that we produce.”

“If you ask what should a normal LDL be? Well, I’ll tell you right now…the best estimate is actually around 38 to 40 mg/dL.”

1. How does the body metabolize lipoproteins and where does LDL-C fit into these processing pathways?

• There are two major pathways through which the body metabolizes lipoproteins. The exogenous fat metabolism pathway includes digestion, absorption, and re-packaging of the lipids that we ingest. Dietary fats are disassembled from energy dense lipid macromolecules into chylomicrons. Chylomicrons are the largest, least dense particles followed by VLDL, IDL, LDL, and HDL. Second, there is the endogenous fat metabolism pathway that allows the liver to synthesize and secrete lipids.
• The structure of LDL-C contains apolipoprotein(B) that serves as a scaffold molecule, with the core compromised of triglyceride and cholesteryl esters, interspersed with phospholipids and cholesterol.
• VLDL is secreted into the central circulation and is acted upon by lipoprotein lipase primarily – but also hepatic lipase and endothelial lipase – to release fatty acid which is used as oxidized fuel by peripheral tissues.
• LDL-C is the energy poor product of triglyceride and fatty acid removal from prior less dense lipoprotein molecules. It is a highly concentrated particle, enriched with cholesterol that cannot be used as fuel by the tissues. It is subsequently converted into bile acids and stored in steroid-producing tissues including the adrenal glands, ovaries, testicles, and placenta. Given its small size, however, it can also traverse the arterial intima of vasculature, ultimately leading to atherosclerosis and cardiovascular disease.
• For more on lipid metabolism and management, enjoy episode #42: Lipid Management with Drs. Ann Marie Navar & Nishant Shah.

2. What is the physiology and function of LDL-C?  How does LDL-C physiology compare between humans and other mammalian species?

• LDL-C transports cholesterol to cells for exogenous uptake and use in bile acid formation and steroid production.
• Most cells have the capacity to produce de novo cholesterol and do not have a strict reliance upon the delivery of extracellular cholesterol via lipoproteins. Cholesterol itself provides a number of important functions within the cell, such as modifying the fluidity of cell membranes, regulating ATP, providing transcriptional control within the nucleus regulating gene expression, and modifying protein functionality.
• In most other mammalian species, studies have demonstrated serum LDL-C levels around 35-50 mg/dL, which is likely more representative of baseline levels in humans without the dietary extremes often accompanying modern diets. Indeed, hunter-gatherer populations are generally very resistant to atherosclerotic cardiovascular disease, and exhibit much lower LDL-C levels.
• Similarly, after the National Cholesterol Education Program published ATPIII (Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults s- Adult Treatment Panel III) in 2001, further analyses investigating the correlation between LDL and ischemic heart disease demonstrated excess hazard starting as low as 38 mg/dL.

3. How do we estimate or measure LDL-C? 

• The Friedewald Equation traditionally allowed for estimation of LDL-C as the [total cholesterol – (HDL – triglycerides/5)], with the last term, triglycerides/5 reflecting an estimate for VLDL-C in the serum.
• Subsequently, the Martin/Hopkins Equation was adopted for the estimation of LDL-C, calculated as the [total cholesterol – (HDL – triglycerides/adjustable factor)], given that VLDL can vary significantly between individuals. This equation more accurately estimates LDL-C levels, particularly with low LDL-C (LDL-C <70mg/dL) or high triglycerides (triglycerides >150mg/dL).
• All measurement equations are measured against the gold standard of direct measurement via preparative ultracentrifugation, though this method is far more costly and time intensive. This method is preferred with triglycerides >400 mg/dL, where estimates become less accurate.
• Non-fasting cholesterol measurements may be more reflective of the “real-world” state as patients are most often post-prandial throughout the day, and are generally recommended as reliable lipoprotein measurement per recent guidelines (the two major exceptions being those undergoing evaluation with a family history of premature cardiovascular disease, and those having eaten a very high-fat meal in the previous 8 hours).

4. How low of an LDL-C is still considered safe? What adverse effects are associated with lower LDL-C levels?

• As above, recent evidence supports lowering LDL-C to <70 mg/dL in those at high cardiovascular risk,  <55 mg/dL in those at very high cardiovascular risk, and even <40 mg/dL in those with a repeat cardiovascular event within two years based on recent U.S. and European  Guidelines.
• The Fourier Trial compared LDL cholesterol reduction with a PCSK9 monoclonal antibody vs placebo and found a 59% reduction from baseline to a median of 30 mg/dL There was no statistically significant difference in adverse events (apart from injection site reactions) in individuals with ultra-low LDL.
• There is no lower limit of LDL cholesterol that is known to be unsafe. Meta-analyses of primary prevention data demonstrate a linear relationship between LDL-C and ischemic coronary event, so the prevailing philosophy currently remains – when it comes to LDL-C, lower is better.
• Modern studies have suggested that lower LDL-C is not associated with risk of increased cognitive impairment or hemorrhagic stroke. The ODYSSEY trial in 2019 demonstrated that for patients with recent ACS and dyslipidemia, PCSK-9 therapy decreased the risk of stroke, regardless of LDL-C levels achieved. The PROSPER trial additionally did not demonstrate any significant difference in cognitive function with statin therapy.
• There is currently no RCT data to suggest impaired immune function or bone density associated with lipid lower therapy. In fact, recent data has suggested that statin therapy may help regulate T-helper cell function and decrease risk of cytokine storm in severe infection.

5. What are future directions for research and clinical practice with regard to lipid lowering therapy?

• Though benefits of lipid therapy have been clearly demonstrated, uptake of LDL-lowering therapy remains inadequate. Only 18-40% of very-high risk patients have LDL-C <70mg/dL. Less than 50% of Medicare patients who sustain MI were on statin therapy at the time of cardiac event. Of individuals who start lipid-lower therapy, more than half will stop therapy within five years.
• Reduced adherence to statin therapy among eligible patients has been directly associated with increased risk of death. In particular, women, minorities, younger adults, and older adults have been found to be less likely to adhere to statins, signaling important disparities among patient populations that must be addressed further.

1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285: 2486–2497.
2. Olsson AG, Angelin B, Assmann G et al. Can LDL cholesterol be too low? Possible risks of extremely low levels. J Intern Med. 2017;281(6):534.
3. Benn M, Nordestgaard BG, Grande P et al. PCSK9 R46L, low‐density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta‐analyses. J Am Coll Cardiol 2010; 55: 2833–42.
4. Grundy SM, Stone NJ, Bailey AL et al. 2018 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143.
5. Members ATF, Piepoli MF, Hoes AW et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol 2016; 23: NP1–96.
6. Cohen JC, Boerwinkle E, Mosley TH et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354: 34–42.
7. Michos ED, McEvoy JW, Blumenthal RS. Lipid Management for the Prevention of Atherosclerotic Carciovascular Disease.  N Engl J Med 2019 Oct 17;381(16):1557-1567.
8. Chien KR. Molecular Basis of Cardiovascular Disease: A Companion to Braunwald’s Heart Disesae. 2nd Ed. 2004.
9. Damask A, Steg PG, Schwartz GG et al. Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial. Circulation. 2020 Feb 25;141(8):624-636.
10. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). European Heart Journal 2020;41:111–188.

Dr. Peter Toth is the Director of Preventive Cardiology at CGH Medical Center in Sterling, IL, and Professor of Clinical Family and Community Medicine at the University of Illinois College of Medicine in Peoria, and adjunct associate professor of medicine, Johns Hopkins University School of Medicine. He received his medical degree from Wayne State University School of Medicine in Detroit, MI, and PhD in Biochemistry from Michigan State University in East Lansing. He has written extensively on the topic of lipids and is Co-Editor of twenty textbooks in preventive cardiology, diabetes, hypertension, and lipidology. Additionally, Dr. Toth is the President of the American Society of Preventive Cardiology, past President of the National Lipid Association, as well as incoming chair of the American Heart Association’s Council on Lipoproteins, Lipid Metabolism, and Thrombosis.

Dr. Jessie Holtzman (@jholtzman3) is an internal medicine resident at the University of California, San Francisco. She received her medical degree from Harvard Medical School, before which she had the time of her life as a Fulbright Scholar doing research in Buenos Aires, Argentina. She ultimately hopes to pursue a career that combines clinical cardiology with an emphasis on women’s cardiovascular health, medical education, and policy making. In her spare time, Jessie loves kayaking on the San Francisco bay, as well as reading about medical device regulation and novel payment models.

• Tommy Das, MD
• Dr. Rick Ferraro
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder) are joined by Dr. LaPrincess Brewer and Dr. Norrisa Haynes for a Narratives in Cardiology episode, with a special introduction by Dr. Sharonne Hayes. They discuss health inequities especially in communities of color, impact of projects utilizing community based participatory research (including FAITH! and SHARP founded by Dr. Brewer and Dr. Haynes respectively), and their experiences as underrepresented minority women physician-scientists.

This special discussion is brought to you in collaboration with the Association of Black Cardiologists (ABC). The ABC’s mission is to “Promote the Prevention and Treatment of Cardiovascular Disease, including Stroke, in Blacks and other Diverse Populations and to Achieve Health Equity for all through the Elimination of Disparities.” You may join and support the ABC at abcardio.org.

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1. What healthcare disparities exist in communities of color?

• The life expectancy of black Americans on average is 3.4 years shorter than that of white Americans. CVD is estimated to explain over 32% of the mortality difference between AA and white men and 43% of the difference between AA and white women. Together these conditions contributed to > 2 million years of life lost in the AA population between 1999-2010. (1)
• The impact of COVID-19 on minority communities has caused disproportionate morbidity and mortality and devastating health and financial hardship. According to the CDC, black Americans are 1.9x as likely as whites to die from COVID-19. (2) Additionally, at the beginning of the pandemic, a staggering 41% of black owned businesses closed due to COVID-19 as compared to 17% of white owned businesses. (3) 

2. Community engagement & Community based participatory research (CBPR) – what is it?

• CBPR often has a public health bend that focuses on and attempts to address social, structural and environmental inequities through active involvement of community members in all aspects of the research process (from conception to implementation). Community partners provide their unique expertise to enhance understanding of the community and facilitate implementation. (4)

3. What is FAITH!?

• The Fostering African American Improvement in Total Health (FAITH) program was started by the phenomenal Dr. LaPrincess Brewer. FAITH is a cardiovascular health and wellness program that uses a CBPR approach to promote heart health in the African American faith-based community.
• Participants in the FAITH program have shown significant improvement in heart health knowledge. Participants have also had improvement in key heart disease risk factors such as blood pressure. The FAITH app was created in collaboration with community members to achieve easy access and easy usability. It provides vital information and a community network that provides support and motivation for participants. 

4. Specifics of SHARP?

• SHARP stands for Safe Haircuts as We Reopen Philadelphia. SHARP was started to assist local barbershops and salons implement proper COVID-19 safety practices to keep their businesses, clients, and staff safe.  In partnership with community members, a safety blueprint was created to meet CDC and Philadelphia Health Department guidelines.  Through donations from UPenn and Accenture, SHARP was able to distribute a significant number of PPE items to 30 businesses in West and Southwest Philadelphia. 
• Additionally, due to the financial toll that the pandemic has had on small businesses, SHARP organized grant writing sessions through the Netter Center at Penn to help the coalition of businesses in West Philadelphia apply for governmental financial relief. Through collaboration with local mental health professionals, SHARP has also been able to offer free therapy to community members. SHARP is currently working with the coalition of businesses to assist them in becoming positive COVID-19 vaccine ambassadors.

5. What is the concept of #MeWho?

• #ME_WHO is a brilliant piece authored by Dr. Michelle Albert that was published in Circulation in 2018. In this piece, Dr. Albert eloquently describes how underrepresented minorities and specifically underrepresented minority women physician-scientists (URMWP) are tasked with maintaining an arduous balance.
• In her words “URMWP are faced with walking a tight rope in academic medicine that requires expertise and excellence in both clinical and scholarly domains, typically with insufficient academic support, social capital, and attainment of senior leadership roles that would turn their zeal and commitment into progress.”
• Dr. Albert then goes on to provide solutions which include: an inclusive ecosystem, academic institutions and professional organizations functioning as drivers of change through partnerships in their communities to elevate the professional and social climate, and federal entities and private funders committing to nurturing a diverse healthcare workforce committed to providing the best possible care to all communities. (5)

The CardioNerds Narratives in Cardiology series features cardiovascular faculty representing diverse backgrounds, subspecialties, career stages, and career paths. Discussing why these faculty chose careers in cardiology and their passion for their work are essential components to inspiring interest in the field.

Each talk will feature a cardiology faculty from an underrepresented group, within at least one of several domains: gender, race, ethnicity, religion, national origin, international graduate status, disadvantaged backgrounds, etc.

Featured faculty will also represent a variety of practice settings, academic ranks, subspecialties (e.g. clinical cardiology, interventional cardiology, electrophysiology, etc), and career paths (e.g. division chief, journal editor, society leadership, industry consultant, etc).

Faculty will be interviewed by fellows-in-training for a two-part discussion that will focus on:

1) Faculty’s content area of expertise
2) Faculty’s personal and professional narrative

As part of their narrative, faculty  will discuss their unique path to cardiology and their current professional role with particular attention to challenges, successes, and advice for junior trainees. Specific topics will be guided by values relevant to trainees, including issues related to mentorship, work-life integration, and family planning.

To help guide this important initiative, the CardioNerds Narratives Council was founded to provide mentorship and guidance in producing the Narratives series with regards to guests and content. The CardioNerds Narratives Council members include: Dr. Pamela Douglas, Dr. Nosheen Reza, Dr. Martha Gulati, Dr. Quinn Capers, IV, Dr. Ann Marie Navar, Dr. Ki Park, Dr. Bob Harrington, Dr. Sharonne Hayes, and Dr. Michelle Albert.

The Narratives Council includes three FIT advisors who will lead the CardioNerds’ diversity and inclusion efforts, including the current project: Dr. Zarina Sharalaya, Dr. Norrisa Haynes, and Dr. Pablo Sanchez.

Dr. La Princess Brewer is an assistant professor and preventative cardiologist at the Mayo Clinic college of medicine. She is an innovative physician-scientist whose research focuses on creating visionary strategies to reduce heart disease and health disparities in minority populations and underserved communities.  Dr. Laprincess Brewer also leads the Fostering African-American Improvement in Total Health (FAITH) program which she started as a cardiology fellow and has since brought to the Mayo clinic.  The Faith program has since grown and evolved.  It is now a mobile application which continues to improve cardiovascular health through the use of technology and digital health but now also focuses on COVID-19 education and COVID-19 mitigation in the African American Community.   Dr. Brewer is also a member of the Association of Black Cardiologists (ABC).

Dr. Norrisa Haynes is a senior cardiology fellow at the University of Pennsylvania (UPenn). She attended Yale University for her undergraduate studies where she received a Bachelor of Science (BS) in Molecular and Cellular Biology. She went on to complete her medical school and internal medicine training at Columbia University College of Physicians and Surgeons. During medical school, she received a Master of Public Health (MPH) from Harvard University. After residency, she worked for Partners in Health (PIH) in Haiti for 2 years at Hôpital Universitaire de Mirebalais (HUM) as a junior attending. During those two years, she also worked as a Harvard Medical School instructor and Brigham hospitalist. After spending 2 years in Haiti, she started cardiology fellowship at UPenn. She is interested in imaging and is currently obtaining a Master of Science in Health Policy (MSHP). Dr. Haynes is a member of the ACC/AHA joint guidelines committee and is a member of UPenn’s Women in Cardiology group (WIC). Dr. Haynes also serves the fellow representative to the board of the Association of Black Cardiologists (ABC).

1. Carnethon MR, Pu J, Howard G, Albert MA, Anderson CAM, Bertoni AG, et al. Cardiovascular health in african americans: A scientific statement from the american heart association. Circulation. 2017 Nov 21;136(21):e393–423.

1. COVID-19 Hospitalization and Death by Race/Ethnicity | CDC [Internet]. [cited 2021 Jan 3]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html

1. More than half of Black-owned businesses may not survive COVID-19 [Internet]. [cited 2021 Mar 5]. Available from: https://www.nationalgeographic.com/history/article/black-owned-businesses-may-not-survive-covid-19

1. Israel BA, Schulz AJ, Parker EA, Becker AB. Review of community-based research: Assessing partnership approaches to improve public health. Annu Rev Public Health. 1998;19:173–202.

1. Albert MA. #me_who anatomy of scholastic, leadership, and social isolation of underrepresented minority women in academic medicine. Circulation. 2018 Jul 31;138(5):451–4.

• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), join cardiology fellows from Indiana University cardiology fellows (Dr. Asad Torabi, Dr. Michelle Morris, and Dr. Sujoy Phookan) to discuss a case of a patient who developed a nagging cough post PCI and is ultimately diagnosed with Dressler Syndrome. This case describes the work up and management of post infarct pericarditis and briefly reviews the dilemma of utilizing triple anti-thrombotic therapy with high dose aspirin in the post myocardial infarction period. Indiana University faculty and expert, Dr. Julie Clary provides the E-CPR for this episode.

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A 56-year-old man with recent anterior STEMI and new heart failure with reduced ejection fraction presented with fevers, persistent cough, and pleuritic chest pain following percutaneous coronary intervention for the past two weeks. He was ultimately found to have post cardiac injury syndrome – post infarct pericarditis (formerly known as Dressler syndrome) with elevated inflammatory markers, a small pericardial effusion, and incidentally noted to have an apical left ventricular thrombus. This case describes the work up and management of post infarct pericarditis and briefly reviews the dilemma of utilizing triple anti-thrombotic therapy with high dose aspirin in the post myocardial infarction period.  

• CXR
• EKG

1. Post cardiac injury syndrome (PCIS) following myocardial infarction can be very debilitating and recurrence is the concern when treatment is not pursued. 

2. Acute pericarditis is a clinical diagnosis which does not require imaging and can have a wide spectrum on presentation ranging from fever/cough to the classic positional chest pain.

3. PCIS following myocardial infarction is less common in the post PCI era but we are starting to see more cases in late presenters.

4. We have good level of evidence to suggest the use of colchicine to reduce the recurrence of PCIS. COPPS and COPPS-2, are two such randomized placebo control trials, which show benefit in the cardiac surgical patient.

5. While triple therapy on high dose aspirin is not discussed in the 2013 ACCF/AHA STEMI guidelines, carefully assess your patient’s bleeding risk and invoke patient shared decision making whenever possible.

1. What is Post-Cardiac Injury Syndrome (PCIS) and what are the clinical manifestations?

• PCIS is an umbrella term for specific clinical scenarios which may result in symptomatic acute pericarditis.
• PCIS encompasses:
  • Post-myocardial infarction pericarditis which may be early or late (Dressler syndrome – the focus of this case)
  • Post-pericardiotomy syndrome (PPS)
  • Post-traumatic pericarditis including traumatic and iatrogenic (following most percutaneous procedures such as ablations, PCI, lead placement, etc).

2. How is PCIS (or post infarct pericarditis) diagnosed?

• This is a clinical diagnosis, made when ≥ 2 of the following are present:
  • Fever without alternative cause
  • Pericarditic or pleuritic chest pain
  • Friction rub
  • Pericardial effusion
  • Pleural effusion with elevated CRP
• Note this is different from the diagnostic criteria for other causes of acute pericarditis which requires 2 of the 4 following features:
  • Pericarditic chest pain
  • Friction rub
  • New widespread ST-elevations or PR depressions on ECG
  • Pericardial effusion (new or worsening)
• Supporting findings for pericarditis include:
  • Elevation of inflammatory markers (CRP, ESR, WBC)
  • Pericardial inflammation on cross sectional cardiac imaging (CT, CMR)

3. What are the complications of not treating Dressler syndrome?

• Imazio et al published an excellent case series in 2009 which answers this question. Overall the prevalence of complications for early and late post-infarct pericarditis was low. No cases of constrictive pericarditis were observed but the incidence of recurrent pericarditis was observed at 3.2%.
• The 2015 ESC pericardial guidelines recommend considering careful follow-up after PCIS to exclude possible evolution towards constrictive pericarditis with echocardiography every 6-12 months according to clinical features and symptoms (Class IIa).

4. What is the evidence for high dose Aspirin in Dressler syndrome?

• This is a class 1b evidence in the 2013 ACCF/AHA STEMI guidelines. This evidence comes from data from a small case series of 24 patients which compared aspirin to indomethacin head-to-head. Overall aspirin was non-inferior with similar bleeding risk. The guidelines recommend the use of high dose aspirin because of NSAIDS may interfere with DAPT and there is also concern regarding scar thinning and infarct expansion. 
• The 2015 ESC pericardial guidelines recommend aspirin as a first choice for anti-inflammatory therapy of post-myocardial infarction pericarditis and those who are already on antiplatelet therapies (Class I).

5. What is the role of colchicine for MI, for chronic coronary disease, for pericarditis, and for PCIS?

• Following MI (without pericarditis): the COLCOT trial showed that colchicine is effective at preventing major adverse cardiac events after MI. In this randomized, double-blind, placebo-controlled trial, a total of 4,745 patients (within 30 days of MI and following intended coronary revascularization) were randomized to colchicine 0.5mg daily or to placebo. After a median follow-up of 22.6 months, there was a significant reduction in the primary efficacy outcome (cardiovascular death, MI, CVA, resuscitated cardiac arrest, or urgent hospitalization for UA leading to revascularization) (HR 0.77, 95% CI 0.61-0.96, p = 0.02).
• Chronic coronary disease (without pericarditis): the LoDoCo2 trial showed that colchicine is effective in reducing major adverse cardiac events in patients with chronic coronary disease. In this randomized, double-blind, placebo-controlled trial, a total of 5,522 patients were randomized to colchicine 0.5mg daily or to placebo. After a median follow-up of 28.6 months, there was a significant reduction in CV mortality, MI, ischemic stroke, or coronary revascularization driven by ischemia events in the treatment arm (HR 0.69, 95% CI 0.57-0.83, p < 0.001).
• Acute pericarditis: the unblinded COPE trial and blinded randomized placebo-controlled ICAP trial demonstrated benefit of colchicine in the first episode of pericarditis, added to NSAID therapy. The CORP trial (blinded RCT) demonstrated benefit of colchicine in recurrent pericarditis.
• Post-pericardiotomy syndrome: the COPPS and COPPS-2 trials showed efficacy of colchicine when initiated 3 days following or 2-3 days preceding surgery respectively, at the cost of increased gastrointestinal side effects.  The 2015 ESC pericardial guidelines recommend:
  • Class IIA: Colchicine added to aspirin or NSAIDs should be considered for the therapy of PCIS, as in acute pericarditis.
  • Class IIA: Colchicine should be considered after cardiac surgery using weight-adjusted doses (i.e. 0.5 mg once for patients ≤70 kg and 0.5 mg twice daily for patients .70 kg) and without a loading dose for the prevention of PPS if there are no contraindications and it is tolerated. Preventive administration of colchicine is recommended for 1 month.

6. What is the recommended approach to triple anti-thrombotic therapy in patient with MI s/p PCI and an indication for anticoagulation?

• The duration for triple therapy should be limited to the shortest duration possible/needed (the duration of aspirin in this regimen remains controversial. In the 2020 ACC expert consensus pathway, a short duration of no more than 30 days is   recommended. Clopidogrel is the P2Y12 inhibitor of choice in this regimen to minimize the risk of bleeding and aspirin should be limited to <100 mg.
• However, the guidelines do not specifically address approach to Dressler syndrome in a post-MI patient treated with PCI who has an indication for anticoagulation (as with apical thrombus in this case) where high dose aspirin would be recommended for pericarditis, DAPT for stent, and warfarin for the thrombus. As with all cases, shared decision making with careful weighing of risks and benefits is advised, in concert with an experienced heart team.

Berman J, Haffajee CI, Alpert JS. Therapy of symptomatic pericarditis after myocardial infarction: retrospective and prospective studies of aspirin, indomethacin, prednisone, and spontaneous resolution. Am Heart J. 1981 Jun;101(6):750-3. doi: 10.1016/0002-8703(81)90610-4. PMID: 7234652. https://pubmed.ncbi.nlm.nih.gov/7234652/

Imazio M, Negro A, Belli R, Beqaraj F, Forno D, Giammaria M, Trinchero R, Adler Y, Spodick D. Frequency and prognostic significance of pericarditis following acute myocardial infarction treated by primary percutaneous coronary intervention. Am J Cardiol. 2009 Jun 1;103(11):1525-9. doi: 10.1016/j.amjcard.2009.01.366. Epub 2009 Apr 8. PMID: 19463510. https://pubmed.ncbi.nlm.nih.gov/19463510/

Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, López-Sendón J, Ostadal P, Koenig W, Angoulvant D, Grégoire JC, Lavoie MA, Dubé MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L’Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16. PMID: 31733140. https://pubmed.ncbi.nlm.nih.gov/31733140/

Imazio M, Trinchero R, Brucato A, Rovere ME, Gandino A, Cemin R, Ferrua S, Maestroni S, Zingarelli E, Barosi A, Simon C, Sansone F, Patrini D, Vitali E, Ferrazzi P, Spodick DH, Adler Y; COPPS Investigators. COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial. Eur Heart J. 2010 Nov;31(22):2749-54. doi: 10.1093/eurheartj/ehq319. Epub 2010 Aug 30. PMID: 20805112. https://pubmed.ncbi.nlm.nih.gov/20805112/

Imazio M, Belli R, Brucato A, Ferrazzi P, Patrini D, Martinelli L, Polizzi V, Cemin R, Leggieri A, Caforio AL, Finkelstein Y, Hoit B, Maisch B, Mayosi BM, Oh JK, Ristic AD, Seferovic P, Spodick DH, Adler Y. Rationale and design of the COlchicine for Prevention of the Post-pericardiotomy Syndrome and Post-operative Atrial Fibrillation (COPPS-2 trial): a randomized, placebo-controlled, multicenter study on the use of colchicine for the primary prevention of the postpericardiotomy syndrome, postoperative effusions, and postoperative atrial fibrillation. Am Heart J. 2013 Jul;166(1):13-9. doi: 10.1016/j.ahj.2013.03.025. Epub 2013 May 6. PMID: 23816016.
https://pubmed.ncbi.nlm.nih.gov/23816016/

Kumbhani DJ, Cannon CP, Beavers CJ, Bhatt DL, Cuker A, Gluckman TJ, Marine JE, Mehran R, Messe SR, Patel NS, Peterson BE, Rosenfield K, Spinler SA, Thourani VH. 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 9;77(5):629-658. doi: 10.1016/j.jacc.2020.09.011. Epub 2020 Nov 26. PMID: 33250267. https://pubmed.ncbi.nlm.nih.gov/33250267/

Klein AL, Abbara S, Agler DA, Appleton CP, Asher CR, Hoit B, Hung J, Garcia MJ, Kronzon I, Oh JK, Rodriguez ER, Schaff HV, Schoenhagen P, Tan CD, White RD. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr. 2013 Sep;26(9):965-1012.e15. doi: 10.1016/j.echo.2013.06.023. PMID: 23998693. https://pubmed.ncbi.nlm.nih.gov/23998693/

• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), Dr. Pablo Sanchez (CardioNerds Ambassador, Stanford University Medical Center), Dr. Maria Pabon (CardioNerds Ambassador, Brigham and Women’s Hospital), and Karen Malacon (Student doctor and LMSA co-chair at Stanford University Medical Center) join Dean for Students at Harvard Medical School, Dr. Fidencio Saldana, for an important discussion about Latinx representation in cardiology. We established the multifaceted benefits of diversity in healthcare, including improving access, cultural competency, and quality of care delivered. We also talked about the need to increase the number of underrepresented minority students in medicine in addition to the importance of removing barriers to improve education. By providing appropriate resources as well as early mentorship and exposure to the medical field, we can address the “leaky pipeline,” or as Dr. Saldana reframed it, “the clogged pipeline.”  Then, we dove into Dr. Saldana’s experiences in medical school, the barriers he overcame, and how his parents’ hard work and generosity motivated him to become the cardiologist he is now. This event hosted the ACC Massachusetts Chapter. Stay tuned for a message by chapter Governor Dr. Malissa Wood.

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 • Quotables • Notes • References • Production Team

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We strive to ensure that we have a diverse set of college students and a diverse set of medical students and residents and fellows. But I think it’s also just as important to ensure that we have the resources to ensure that those individuals that we’ve recruited and have done so hard to recruit, continue to succeed.

I’ve realized that you can teach mentoring, you can teach advising. And I think it’s important to be able to create that culture and expectation. Some people may be a little bit better at it than others, but I think it’s important to place an emphasis on that at each level of training, so that you can train to be a better mentor and a better advisor.

1. How is the LatinX representation in medicine compared to in the general population?

• Based on the most recent data from the US census Bureau, as of 2019, the Hispanic proportion of the US population is about 18.5%.
• A recent report by the AAMC showed that for the academic year 2020-21, of around 22,000 medical school matriculants, only 11% were from LatinX background, although this number was higher compared to 2017 where only 9.8% of the matriculants were of LatinX origin.  

2. How does increasing workforce diversity improve quality of care?

• Cultural competency forms an important cornerstone of high-quality and equitable care for a diverse population, and it is learned not by lecture but by exposure, experience, and atmosphere.
• Medicine involves not only knowledge but meaningful connection and having a physician with a common background enhances the patient-doctor interaction by a spectrum of constructive effects.
• Inasmuch as research questions are guided by interests of investigators, the inclusion of underrepresented minorities among the pool of investigators stands to better delineate problems and articulate solutions. Actuating the gears of change at state/local governments and health systems to solve issues of access and quality of care will be only benefited by inclusion of medical-trained underrepresented minorities at the table. 

3. How do can we promote diversity in fellowship programs?

• Participate in and support efforts to promote recruitment of underrepresented minorities for residency and fellowship programs as well as retention at the faculty level.
• Participate in initiatives focused on mentoring underrepresented minorities early on (high school or college students).
• Educate ourselves and others about the barriers that underrepresented minorities must overcome such as inadequate housing, food insecurity, and/or financial support.

4. What is the role of mentorship in diversity and inclusion?

• Mentorship is one of the pillars to diversify our health care workforce. Mentoring one single medical student will translate into exponential beneficial effects for patients.
• Mentors can help to overcome internal and systemic barriers that students may encounter during their path as early as during high school and college education.
• Mentorship does not stop after training is complete and should continue at the faculty level.
• Mentorship and advising can be taught and should be an expectation during training. 

Weinstein DF, Saldana F. DACA and the Dream of Becoming a Physician. N Engl J Med. 2017 Nov 16;377(20):1913-1915. doi: 10.1056/NEJMp1713102. Epub 2017 Oct 25. PMID: 29068757.

Cohen JJ, Gabriel BA, Terrell C. The case for diversity in the health care workforce. Health Aff (Millwood). 2002 Sep-Oct;21(5):90-102. doi: 10.1377/hlthaff.21.5.90. PMID: 12224912.

AAMC, Matriculants to US medical schools by race. 10/26/2020.    https://www.aamc.org/media/6031/download

• Daniel Ambinder, MD
• Amit Goyal, MD
• Gurleen Kaur, MD

CardioNerds (Amit Goyal and Daniel Ambinder), Cardio-OB series co-chair and University of Texas Southwestern Cardiology Fellow, Dr. Sonia Shah, and episode lead and Columbia University Cardiology Fellow Dr. Ersilia DeFilippis discuss hypertensive disorders of pregnancy (HDP) with Dr. Jennifer Lewey from the University of Pennsylvania.

In this episode, we cover chronic hypertension, gestational hypertension, and pre-eclampsia—all of which encompass HDP and complicate approximately 5-10% of all pregnancies. We also review risk factors for HDP, diagnostic criteria, peripartum and postpartum management, and much more! Be sure to tune in to hear Dr. Lewey discuss the future impact of HDP on cardiovascular disease for women later in life and strategies that can help improve care.

Finally Dr. DeFilippis shares her perspectives from her ACC.org FIT Section article titled “Shattering the Glass” including strategies to shattering the glass and tackling imposter syndrome in improving the representation of women in medicine.

Audio editing by CardioNerds Academy Intern, Leticia Helms.

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1. To make a diagnosis of HDP, blood pressure should be measured on at least 2 occasions at least 4 hours apart.
2. Hypertension diagnosed before 20 weeks gestation is considered chronic hypertension whereas hypertension after 20 weeks is categorized as gestational hypertension.
3. Always check for warning signs for pre-eclampsia!
4. One of the key treatments for pre-eclampsia is delivery but pre-eclampsia can occur still in the postpartum period.
5. Aspirin use in pregnancy during second and third trimesters can reduce the risk of pre-eclampsia among women at risk.

“Ideally a lot of these conditions come down to prevention and addressing potential cardio-obstetrics issues before they reach the cardio-obstetrics specialist.”

“Blood pressure can continue to be elevated even after delivery.”

“Pregnancy complications not only increase cardiovascular risk in the middle age population but also in the postmenopausal population.”

“Women feel so relieved when they know that their care team is dedicated to taking care of women with cardiovascular disease when they are pregnant.”

1. Why should CardionNrds learn and know about hypertensive disorders of pregnancy?

Hypertensive disorders of pregnancy (HDP) complicate about 5-10% of all pregnancies. HDP is a term that encompasses chronic hypertension, gestational hypertension, pre-eclampsia, and pre-eclampsia superimposed on chronic hypertension. Women with history of HDP are at increased risk for stroke, ischemic heart disease, and cardiovascular death later in life. It is important to include obstetric history as part of our assessment of cardiovascular risk.

This obstetric history should include the number of pregnancies, history of gestational diabetes, gestational hypertension, history of pre-eclampsia as well as history of pre-term birth.

Following delivery, these women need close monitoring for development of chronic hypertension as well as primary prevention of cardiovascular disease.

2. How is gestational hypertension distinguished from chronic hypertension?

The key factor in distinguishing gestational hypertension from chronic hypertension is the timing of diagnosis. Before 20 weeks gestation, elevated blood pressure (defined as a reading > 140/90 on two occasions at least 4 hours apart) is considered chronic hypertension. After 20 weeks gestation, elevated blood pressures signify a pregnancy-induced process, namely gestational hypertension or pre-eclampsia if blood pressure elevation is severe enough or there is evidence of end-organ damage.

Blood pressure is often lower in the 1st and 2nd trimesters due to lower systemic vascular resistance. We think the process of gestational hypertension and pre-eclampsia result from how spiral arteries implant in the uterus. There are a whole host of local factors that lead to an increase in blood pressure later on in pregnancy.

3. What are warning signs of pre-eclampsia?

Pre-eclampsia is diagnosed in the setting of high blood pressure, usually after 20 weeks, in the setting of proteinuria or end-organ dysfunction. End-organ dysfunction most commonly includes thrombocytopenia, transaminitis, right upper quadrant pain, headaches, pulmonary edema, and symptoms and signs that are not explained by other causes. Notably, blood pressure readings greater than > 160/110 mm Hg are sufficient for the diagnosis in the absence of other findings.

4. What are risk factors for pre-eclampsia or pre-eclampsia superimposed on chronic hypertension?

Risk factors for pre-eclampsia include a personal or family history of pre-eclampsia in prior pregnancies, chronic hypertension, older age, multiple gestation, obesity, and Black race.

5. When do we start treatment for hypertension during pregnancy?

For women who are newly diagnosed with hypertension during pregnancy, the threshold to begin treatment is 160 mm systolic and 110 mm diastolic. The caveat to this is for women with known cardiovascular disease or other comorbidities, a lower blood pressure goal should be targeted closer to 120-130 mm Hg systolic over 80 mm diastolic. Typically, a higher blood pressure is tolerated in order to avoid uteroplacental hypoperfusion which can impact the growth of the baby.

The CHIPS randomized trial was published in the NEJM in 2015 and compared less tight control (targeting diastolic blood pressure of 100 mm Hg) or tight control (targeting diastolic blood pressure of 85 mm Hg). Although tight control decreased the rate of severe maternal HTN, there was no significant difference in the risk of pregnancy loss or overall maternal complications.

1. How can we modify risk in women with hypertension during pregnancy?

Low dose aspirin use (81 mg daily) in pregnancy during second and third trimesters can reduce the risk of pre-eclampsia among women at risk. The USPTF recommends the use of aspirin as preventative medication after 12 weeks of gestation in women at high risk for pre-eclampsia (Grade B). Risk factors that qualify someone as high risk include history of pre-eclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal disease, and/or autoimmune disease. ACOG also recommends aspirin prophylaxis initiated between 12 and 28 weeks of gestation, optimally before 16 weeks and continued daily until delivery.

7. What is the best approach to anti-hypertensive medication use in pregnancy?

First line agents used during pregnancy for treatment of hypertension include labetalol and nifedipine. Hydralazine is a second-line agent that may be used. Although methyldopa classically appears on board exams, it is less effective and has side effects including depression and fatigue.

For women with a history of hypertension prior to pregnancy that is well-controlled on agents such as amlodipine or hydrochlorothiazide, these can be continued since limited evidence suggests they are safe although there is just less available evidence.

For women on angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid antagonists, these must be stopped given their teratogenic effects.

This table from a recent JACC review by Halpern et al summarizes nicely safety of antihypertensive medications in pregnancy and during breastfeeding.

8. How do we treat pre-eclampsia?

Treatment of pre-eclampsia depends on severity and gestational age. Management is primarily two-fold: 1) using intravenous medications such as labetalol and hydralazine to lower the blood pressure; 2) magnesium sulfate for seizure prophlaxis. Delivery may help resolve the symptoms of pre-eclampsia and may be considered following 37 weeks gestational age.

Halpern et al. Use of Medication for Cardiovascular Disease During Pregnancy: JACC State-of-the-Art Review. JACC 2019;73(4):457-476.

ACOG Committee Opinion. Low Dose Aspirin-Use During Pregnancy. July 2018.

Magee et al. Less-Tight versus Tight Control of Hypertension in Pregnancy. NEJM 2015;372:407-417.

Wang Y-X, Arvizu M, Rich-Edwards JW, et al. Hypertensive disorders of pregnancy and subsequent risk of premature mortality. J Am Coll Cardiol. 2021;77(10):1302-1312. doi.org/10.1016/j.jacc.2021.01.018.

Dr. Jennifer Lewey is an Assistant Professor at the  University of Pennsylvania, Director of Penn Women’s Cardiovascular Health Program, and Co-Director of the Pregnancy and Heart Disease Program.

Ersilia DeFilippis is a third-year general cardiology fellow at Columbia University Irving Medical Center in New York City. She will be beginning her fellowship in advanced heart failure and transplant cardiology next academic year at Columbia. Her research and clinical interest are in sex differences in advanced heart failure management and outcomes, racial disparities in heart failure outcomes, and cardio-obstetrics.

• Natalie Stokes, MD
• Sonia Shah, MD
• Amit Goyal, MD
• Daniel Ambinder, MD