Cardionerds: A Cardiology Podcast

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Patrick Azcarate and Dr. Antoinette Birs from the University of California San Diego along with a guest host Dr. Christine Shen from Scripps Health for a hike along Torrey Pines. They discuss a case of a 30-year-old man with a history of malignant thymoma status post two partial lung resections and radiation for pleural/pulmonary metastasis, as well as a history of myasthenia gravis on rituximab, and Ig deficiency on IVIG presents with progressive exertional chest pain. We focus on the differential diagnosis of patients with a history of chest radiation exposure and dive into the complex management and surveillance for patients with radiation associated cardiac disease (RACD). The E-CPR is provided by Dr. Milind Desai (multimodality cardiovascular imaging expert, Director of Clinical Operations, Director of Center for HCM, Medical Director for Center for Aortic Diseases, and Medical Director for Center for Radiation Heart Disease at the Cleveland Clinic). Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls – Notes – References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media TTE TTE TTE TTE AP Cranial Pre PCI LAO Caudal Pre PCI RAO Caudal Pre PCI RAO Cranial Pre PCI AP cranial Post PCI Episode Teaching Pearls – radiation associated cardiac disease Radiation-associated cardiac disease (RACD) is a heterogeneous disease that can manifest several years, or decades following radiation exposure to the chest and is associated with high morbidity and mortality. Given the non-specific or vague symptoms, one of the greatest challenges for this patient population may be diagnosing RACD which requires high clinical suspicion.  In patients with a history of chest radiation, we should remember to ask three important questions: 1. What was the total dose of radiation given? 2. How long ago was radiation therapy administered? 3. Was the heart exposed? A cumulative dose of >30 Gray (Gy) chest radiation significantly increases the risk of RACD long-term, but cardiac damage can occur at even lower doses.  Effects from chest radiation can take years to become clinically detectable. Screening for radiation induced coronary artery disease with stress testing should start 5 years following XRT and in low-risk patients (without risk factors for typical coronary artery disease) and continue at 5-year intervals, and 2-year intervals in high-risk patients. Valvular heart disease surveillance should begin 10 years post XRT and can be accomplished with echocardiogram.  Regarding revascularization planning, a Heart Team approach is recommended. However, percutaneous intervention is preferred over bypass surgery in most cases. Notes – radiation associated cardiac disease 1. What is Radiation-Associated Cardiac disease (RACD)? A spectrum of disease that can affect any part of the heart and typically develops anywhere from 5 to 20 years after radiation. It may present with non-specific or vague symptoms. Manifestations include myocarditis, pericarditis (typically early in the course) and well as long term sequela such as myocardial fibrosis, valvular heart disease (regurgitation or stenosis), pericardial disease, vasculopathy (CAD), conduction system disease. Radiation may impact any tissue of the heart: Vascular: microvascular, coronary artery disease, macrovascular (ascending aorta) Valvular: has a longer latency ~10-20 years with the left sided valves being more commonly affected; Aorto-mitral curtain thickening/calcification is a hallmark of previous heart radiation and associated with higher mortality  Conduction: Sick sinus syndrome, AV nodal block, atrial fibrillaiton; infra-nodal conduction disease and RBBB are common. Myocardial: fibrosis in the myocardium leading to HFpEF, or HFrEF; XRT + anthracycline is thought to be synergistic. Pericardial: chronic pericardial inflammation, scarring, calcification, restrictive physiology. Constrictive pericarditis from radiation has a particularly poor prognosis given often concurrent myocardial involvement. 2. What is the Pathophysiology of RACD? The severity of disease is related to total radiation dose, fraction size and volume of the heart in the radiotherapy field. The resulting cell damage leads to activation of the acute inflammatory cascade and pro-fibrotic milieu. 3. What are the additional risk factors for RACD? Therapy-related risk factors: Net dosage (dependent on cancer type and tumor site) > 30Gy received by the heart. Proximity to heart to the radiation field. Concomitant chemotherapy – anthracyclines may particularly have a radiation sensitizing effect, thereby increasing the risk of RACD. Patient-related risk factors: Life expectancy – younger age at the time of radiation and a good cancer prognosis, as these patients may have more time to manifest the longer-term sequelae of RACD. Presence of traditional cardiovascular risk factors 4. How common is RACD?  RACD is most often seen in those receiving chest radiation for breast cancer (particularly left sided), Hodgkin Lymphoma, lung cancer and esophageal cancers. There is a distinct population presenting with latent symptoms from treatment with wide-field radiation of Hodgkin lymphoma that was more commonly practiced 20-40 years ago. Prevalence of radiation associated cardiomyopathy is ~10% based on population studies although difficult to determine given the heterogeneity of presentation and under-recognition.  Valvular abnormalities in 7-39% at 10 years, 12-60% at 20 years  Mitral and aortic valves are most affected; symptoms arise 1-2 decades after radiation and later than CAD; AR in 60% vs 4% at 20 years vs 10 years post treatment.  Aorto-mitral curtain thickening/calcification is a hallmark of previous heart irradiation, and its extent is strongly associated with mortality in subjects undergoing cardiac surgery.  Radiation induced coronary vasculopathy has a prevalence of 85%.  5. What is Radiation induced coronary artery disease (RICAD)?   Pathophysiology: inflammatory plaque, with accumulation of myofibroblasts, resulting in intimal proliferation with aggregation of lipid-rich macrophages; high collagen and fibrin content like accelerated atherosclerosis; doses of > 0.50 Gy can initiate atherosclerosis and affects micro and macro vasculature. Angiographically: Ostial or proximal epicardial coronary lesions of the anterior and central vessels are most common (left main trunk, proximal LAD, mid diagonal, or RCA) given the location of the heart in the chest. Lesions are often severe, proximal, and diffuse. They are typically long, smooth, concentric, and tubular and may require intravascular ultrasound (IVUS) for diagnosis as they can appear normal on coronary angiography (lumenography). 6. What are different types of radiation?   3D vs Intensity modulated radiation therapy (IMRT): both are x-ray-based radiation Proton therapy: Unlike x-rays which go all the way through the body, protons are charged and can go to a specified depth causing less scatter radiation 7. What techniques may be used to reduce cardiac exposure to the radiotherapy field? ABC device, breathing techniques such as deep inspiratory breath hold (DIBH) which pulls the heart more inferiorly in the chest and allows treatment of the upper mediastinum with less cardiac exposure, shielding  8. What are the surveillance recommendations?  The risk of RACD is 7.5% per Grey Unit (Gy) and is constant, beginning several years after exposure and persists for at least 2-3 decades (>50% of excess ischemic events occurring >10 years after RT). Those who will receive >30 Gy may warrant cardiology consultation prior to treatment Screening for CAD: 5 years after radiation exposure Screening for valvular disease: 10 years after exposure with 5-year surveillance intervals  9. What is the recommended approach for revascularization for RICAD? PCI is generally preferred if feasible over bypass given chest radiation as this patient group has increased risk of complications from bypass surgery related to severely calcified aorta, possible radiation injury to the IMAs, restrictive lung disease, difficulty weaning patient from a ventilator, and lack of intra-thoracic lymphatics  References Desai MY, Jellis CL, Kotecha R, Johnston DR, Griffin BP. Radiation-Associated Cardiac Disease: A Practical Approach to Diagnosis and Management. JACC Cardiovasc Imaging. 2018 Aug;11(8):1132-1149. doi: 10.1016/j.jcmg.2018.04.028. PMID: 30092970. https://www.jacc.org/doi/abs/10.1016/j.jcmg.2018.04.028 Desai MY, Windecker S, Lancellotti P, Bax JJ, Griffin BP, Cahlon O, Johnston DR. Prevention, Diagnosis, and Management of Radiation-Associated Cardiac Disease: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Aug 20;74(7):905-927. doi: 10.1016/j.jacc.2019.07.006. https://www.jacc.org/doi/full/10.1016/j.jacc.2019.07.006 Cuomo JR, Javaheri SP, Sharma GK, Kapoor D, Berman AE, Weintraub NL. How to prevent and manage radiation-induced coronary artery disease. Heart. 2018 Oct;104(20):1647-1653. doi: 10.1136/heartjnl-2017-312123. Epub 2018 May 15. PMID: 29764968; PMCID: PMC6381836. https://heart.bmj.com/content/104/20/1647.long Wu W., Masri A., Popovic Z.B.et al. : “Long-term survival of patients with radiation heart disease undergoing cardiac surgery: a cohort study”. Circulation 2013; 127: 1476. https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.113.001435 CardioNerds Case Report Production Team Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

Dr. Anu Lala, a leading expert in advanced heart failure, dives into the intricacies of cardiogenic shock. She discusses the essential protocols for initial assessment and the importance of a Shock Team in providing optimal care. The conversation highlights the collaboration among specialists for comprehensive evaluations and emphasizes recognizing patients as unique individuals. Dr. Lala also addresses the emotional and ethical dimensions of managing critical cases, offering insights into the profound human experience of healthcare.

In this episode, CardioNerds (Amit Goyal), Cardio-OB series co-chair and UT Southwestern cardiology fellow, Dr. Sonia Shah, and episode lead fellow, Dr. Laurie Femnou (UT Southwestern) are joined by Dr. Michael Luna (UT Southwestern) to discuss cardiovascular interventions during pregnancy. We discuss practical considerations for performing coronary angiography and valvular interventions in the pregnant patient, the timing and indication of procedures, and ways to minimize radiation exposure to both mom and baby. Audio editing by CardioNerds Academy Intern, Hirsh Elhence. This episode is made possible with support from Panacea Financial. Panacea Financial is a national digital bank built for doctors by doctors. Visit panaceafinancial.com today to open your free account and join the growing community of physicians nationwide who expect more from their bank. Panacea Financial is a division of Primis, member FDIC. Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Cardio-Obstetrics Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls- Cardiac Interventions during Pregnancy Attempt should be made to manage pregnant patients with valvular disease with medical therapy, and cardiac interventions during pregnancy should be considered a last resort. Ideally, procedures in the gravid patient should be performed after 20 weeks gestation to minimize fetal risk.  Specific ways to minimize radiation to the pregnant patient and fetus in the catheterization lab include: using an abdominal shield, radial access for coronary procedures, proper positioning of the C-arm to avoid extreme angulation, using collimation, and minimizing fluoroscopic time, frame rate, and use of cine-acquisition. When appropriate, intracoronary imaging modalities (ie. IVUS or OCT) should also be considered. Fetal monitoring should be performed during any cardiac intervention in the pregnant patient Multidisciplinary involvement and contingency planning are critical for the success of any high-risk cardiac intervention in the pregnant patient. Quatables – Cardiac Interventions during Pregnancy “Meetings including all providers— our cardiac surgical colleagues, cardiac anesthesiologists, and our obstetrics team—in the care of [pregnant] patients has to be had well ahead of a cardiac procedure to plan every detail.” Show notes – Cardiac Interventions during Pregnancy 1. What are special considerations for performing a balloon valvuloplasty in a pregnant patient with mitral stenosis?  In pregnant patients with severe mitral stenosis who cannot be adequately managed with medical therapy, percutaneous balloon mitral valvuloplasty (PMBV) is the treatment of choice given the high risk of morbidity and fetal loss with cardiac surgery. Ideally, procedures in the gravid patient should be performed after 20 weeks gestation to minimize risk to the fetus.  Assessment of valve anatomy and consideration of the Wilkin’s score are especially important in pregnant patients to minimize the risk of peri-procedural complications. PBMV should performed at experienced centers with cardiac surgery and MFM available. Complications of PBMV are rare but include atrial perforation, cardiac tamponade, arrhythmias, emboli, mitral regurgitation, hypotension and maternal death. Mechanical support should be readily available and a delivery strategy in place in case there is sudden maternal or fetal deterioration. 2. What are ways to minimize radiation exposure in the catheterization lab to the pregnant patient and fetus? The general principle for imaging during pregnancy is similar to imaging for the general population, with the goal of radiation exposure being as low as reasonably achievable (ALARA). The mean radiation exposure to the unshielded abdomen is 1.5 mGy, and <20% of this reaches the fetus.  Specific ways to minimize radiation to the pregnant patient and fetus in the catheterization lab include the following: using an abdominal shield, radial access for coronary procedures, proper positioning of the C-arm to avoid extreme angulation, using collimation, and minimizing fluoroscopic time, frame rate, and use of cine-acquisition. When appropriate, intracoronary imaging modalities (ie IVUS or OCT) should also be considered. 3. What should we know about coronary angiography and revascularization in the pregnant woman? According to a large US-based study of 859 patients presenting with acute myocardial infarction during pregnancy and the postpartum period, less than half of patients undergo cardiac catheterization. In stable, low-risk NSTEMI, a non-invasive approach should be considered per ESC guidelines. In pregnant patients who present with STEMI, PCI is the preferred revascularization strategy. Radial access should be used if possible, as femoral artery access involves direct pelvic radiation. In pregnancy-associated SCAD, enhanced vascular vulnerability should be considered when performing angiography, from obtaining access to engaging the coronary ostia. Fetal monitoring should be performed during any cardiac intervention in the pregnant patient 4. What is the role of mechanical support in the management of peripartum patients with cardiogenic shock? Urgent intervention with mechanical assist support, including intra-aortic balloon pump, impella, and VA-ECMO, may be necessary in rare circumstances. Prompt assessment of hemodynamics can be helpful to determine the level of support needed. Axillary access may be considered in patients with favorable anatomy. References Patel C, Akhtar H, Gupta S, Harky A. Pregnancy and cardiac interventions: What are the optimal management options? Journal of Cardiac Surgery, 2020. 35(7): 1589-1596. Regitz-Zagrosek V, Lundqvist CB,  Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). European Heart Journal, 2011. 32, 3147–3197 doi:10.1093/eurheartj/ehr218 Guest Profiles Dr. Michael Luna Dr. Michael Luna is an associate professor of cardiology at UT Soutwestern trained in interventional cardiology, with additional focused training in congenital heart disease. He specializes in adult congenital heart defects, heart valve disorders, and complex coronary artery disorders. Dr. Luna also serves as one of the supervising attendings in the Parkland Congenital Heart Disease Fellow’s Clinic. Dr. Laurie Femnou Dr. Laurie Femnou Mbuntum is currently a general cardiology fellow at The University of Texas Southwestern. She completed her undergraduate degree at The University of Maryland Baltimore County. She then moved down South to complete residency at The University of Texas Southwestern where she stayed for cardiology fellowship where she is planning to stay for advanced training in interventional cardiology. She has a special interest in cardio obstetrics and figuring out ways to reduce cardiovascular maternal death. When not in the hospital, she loves spending time with her two boys and learning more about makeup artistry. CardioNerds Cardioobstetrics Production Team Natalie Stokes, MD Sonia Shah, MD Amit Goyal, MD Daniel Ambinder, MD

Dr. Michelle Kittleson, a leading expert in cardiology, discusses challenging cases of hypertrophic cardiomyopathy. Topics covered include advising patients with a family history of HCM, shared decision making in treatment options, use of implantable loop recorders, interpretation of imaging studies, and the global perspective in HCM patient care. Anticoagulation in HCM is also highlighted.

CardioNerds (Amit Goyal and Daniel Ambinder) join CardioNerds Ambassadors Dr. Pablo Sanchez (FIT, Stanford University) and Dr. Christine Shen (FIT, Scripps Clinic) for a discussion with Dr. Bob Harrington (Interventional Cardiologist, Professor of Medicine, and Chair of the Department of Medicine at Stanford University) about diversity and inclusion in the field of cardiology. This episode discusses Dr. Harrington’s broader approach to mentorship, sponsorship, and allyship; and particularly how (and why) he used his position as the president of the American Heart Association to advocate against all-male panels, or “manels.” Listen to the episode to learn the background and motivations behind his evidence-based efforts to make Cardiology a more inclusive field. Special message by California ACC State Chapter President, Dr. Jamal Rana. 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. Video Version • Notes • References • Production Team Claim free CME just for enjoying this episode! There are no relevant disclosures for this episode. The PA-ACC & CardioNerds Narratives in Cardiology PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Video version – Diversity and Inclusion https://youtu.be/SnUadVRhH70 Quotables – Diversity and Inclusion “If senior men don’t change the field, it’s not going to change. We have the senior positions. We have to change it.” “You’re missing talent. You’re missing talent of the women who have decided not to go into Cardiology. I say to a lot of my male colleagues…don’t you care about the health of our specialty? Don’t you want the very best people going into it?” “How great is that–to open up an artery in the middle of the night?… What could be better than that?…Why would you not want to be a cardiologist? Frankly, maybe the field is not so friendly to women…And that bothers me greatly because I love the specialty.” “To those who have been given much, much is expected. That’s what people like me should do.” Dr. Bob Harrington Show notes – Diversity and Inclusion What are the gender disparities in the field of Cardiology? 45.8% of residents and fellows in ACGME-accredited programs are women. 14.9% of cardiologists are women. 8% of interventional cardiologists are women [1]. 30.6% of male faculty were full professors, while 15.9% of female faculty are full professors [2]. Men are more likely to be influenced by positive attributes of a field, while women are more likely to be influenced by negative attributes [3]. 3% of percutaneous coronary interventions in the United States are performed by female operators [4]. What is mentorship, sponsorship, and allyship? A mentor provides advice and helps someone develop a skill. A sponsor is an advocate who helps someone secure career advancement opportunities. An ally partners with people, utilizing their power and influence to champion the rights of others [5]. According to some studies, women report less sponsorship experiences than men. Additionally, in women it seems to translate less frequently into experiences that further their career (speaking engagements, serving on editorial boards, etc) [6]. “I’m a mentor to a few people, I’m a sponsor to many, and I’m an ally to all.” – Dr. Bob Harrington Why is a diverse cardiovascular workforce so important? Teams that are diverse pursue innovative and creative solutions. Medicine requires meaningful connections and having a physician with a common background enhances the patient-doctor interaction by a spectrum of constructive effects. Minority groups are less likely to be treated with effective cardiac medications [7]. There continue to be barriers in clinical trials to include diverse and underrepresented patients [8]. A diverse workforce of clinical scientists is crucial to promoting diversity in clinical trials, including understanding the problem, asking the right questions, and proposing solutions [9]. References AAMC 2019. Physician Specialty Data Report. Accessed November 18, 2021. Blumenthal DM, Olenski AR, Yeh RW, et al. Sex Differences in Faculty Rank Among Academic Cardiologists in the United States. Circulation. 2017;135(6):506-517. doi:10.1161/CIRCULATIONAHA.116.023520 Yong CM, Abnousi F, Rzeszut AK, et al. Sex Differences in the Pursuit of Interventional Cardiology as a Subspecialty Among Cardiovascular Fellows-in-Training [published correction appears in JACC Cardiovasc Interv. 2019 Apr 8;12(7):695]. JACC Cardiovasc Interv. 2019;12(3):219-228. doi:10.1016/j.jcin.2018.09.036 Wang TY, Grines C, Ortega R, et al. Women in interventional cardiology: Update in percutaneous coronary intervention practice patterns and outcomes of female operators from the National Cardiovascular Data Registry®. Catheter Cardiovasc Interv. 2016;87(4):663-668. doi:10.1002/ccd.26118 Sharma G, Narula N, Ansari-Ramandi MM, Mouyis K. The Importance of Mentorship and Sponsorship: Tips for Fellows-in-Training and Early Career Cardiologists. JACC Case Rep. 2019;1(2):232-234. Published 2019 Aug 21. doi:10.1016/j.jaccas.2019.06.007 Patton EW, Griffith KA, Jones RD, Stewart A, Ubel PA, Jagsi R. Differences in Mentor-Mentee Sponsorship in Male vs Female Recipients of National Institutes of Health Grants. JAMA Intern Med. 2017;177(4):580-582. doi:10.1001/jamainternmed.2016.9391 Tran HV, Waring ME, McManus DD, et al. Underuse of Effective Cardiac Medications Among Women, Middle-Aged Adults, and Racial/Ethnic Minorities With Coronary Artery Disease (from the National Health and Nutrition Examination Survey 2005 to 2014). Am J Cardiol. 2017;120(8):1223-1229. doi:10.1016/j.amjcard.2017.07.004 Clark LT, Watkins L, Piña IL, et al. Increasing Diversity in Clinical Trials: Overcoming Critical Barriers [published correction appears in Curr Probl Cardiol. 2021 Mar;46(3):100647]. Curr Probl Cardiol. 2019;44(5):148-172. doi:10.1016/j.cpcardiol.2018.11.002 Poppas A, Albert MA, Douglas PS, Capers Q 4th. Diversity and Inclusion: Central to ACC’s Mission, Vision, and Values. J Am Coll Cardiol. 2020;76(12):1494-1497. doi:10.1016/j.jacc.2020.08.019 Production Team Dr. Gurleen Kaur Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), are joined by guest host Dr. Alex Pipilas (CardioNerds Ambassader, Boston University), and Cleveland Clinic fellows, Dr. Gary Parizher, Dr. Ambreen Ali, and Dr. Tiffany Dong. They discuss a case of an 18-year-old man with Autism Spectrum Disorder presented with advanced nonischemic dilated cardiomyopathy. Due to anxiety, he was unable to tolerate right heart catheterization, and the initial evaluation for advanced heart failure therapies was deferred. With assistance from a multidisciplinary team, catheterization was successful, and he underwent cardiac transplantation. Faculty experts, Dr. Richard Dane Meredith (Cardiovascular Imaging, Mission healthcare), Dr. Julie Niezgoda (Congenital Cardiac Anesthesiologist, CCF), and Dr. Ran Lee (Critical Care Cardiology and Advanced HF/Transplant Cardiologist, CCF) provide the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Dr. Leticia Helms. Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls – Notes – References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media Episode Teaching Pearls – Heart Failure with Autism Spectrum Disorder Autism spectrum disorder should not be regarded as a contraindication to organ transplantation. Respect for patient discomfort with procedures, and efforts to mitigate that discomfort, are essential. A multidisciplinary team approach, especially one utilizing allied health support services, is important to provide care to adolescent patients with advanced organ dysfunction, particularly those with developmental disabilities. Notes – Heart Failure with Autism Spectrum Disorder Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and the presence of restricted, repetitive patterns of behaviors, interests, or activities (2). In 2016 the CDC estimated one in 54 children age 8 had ASD (3). Despite ASD’s prevalence, studies of organ transplantation in children and adolescents with developmental disabilities are lacking. Guidelines from the International Society for Heart Lung Transplantation indicate that heart transplantation cannot be recommended in patients suffering from severe cognitive-behavioral disabilities (4). However, the definition of “severe” is not clear, so the assessment of severity of a cognitive impairment, as well as whether the impairment constitutes a contraindication to organ transplantation, falls to healthcare providers on a case-by-case basis.             Cardiac transplantation in a patient with ASD has been documented previously (5). Nonetheless our case represents an important example of advocacy for lifesaving care in patients with developmental disability. Without any one component of the team taking care of our patient, including physicians and allied healthcare providers, he would have died of refractory cardiogenic shock. However, with individualized care and a multidisciplinary combined effort, his providers were able to overcome the obstacles posed by his ASD and deliver indicated interventions. References – Heart Failure with Autism Spectrum Disorder 1.  Baran, David A., et al. “SCAI clinical expert consensus statement on the classification of cardiogenic shock” Catheterization and Cardiovascular Interventions 94.1 (2019): 29-37. 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 5th edition. Arlington, VA: American Psychiatric Association, 2013. 3. Baio J, Wiggins L, Christensen D, et al. Prevalence of Autism Spectrum Disorder among children aged 8 years – Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Surveillance Summaries 2018; 67:1-23. 4. Mehra M, Canter C, Hannan M, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung Transplant 2016; 35:1-23. 5. Bailey D, Schneider L, Maeda K, et al. Orthotopic heart transplant in a child with nonverbal autism. Austin J Autism & Relat Disabil 2016;2:1017. 6. Chen Y, Shlofmitz E, Khalid N, et al. Right Heart Catheterization-Related Complications: A review of the literature and best practices. Cardiol Rev 2020;28:36-41. CardioNerds Case Report Production Team Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

Pregnancy is a hypercoagulable state associated with increased risk of thromboembolism. Managing anticoagulation during pregnancy has implications for both the mother and the fetus. CardioNerd Amit Goyal joins Dr. Akanksha Agrawal (Cardiology Fellow at Emory University), Dr. Natalie Stokes (Cardiology Fellow at UPMC and Co-Chair of the Cardionerds Cardio-Ob series), and Dr. Katie Berlacher (Program Director of the Cardiovascular Disease Fellowship and Director of the Women’s Heart Program at UPMC) as they discuss the common indications for anticoagulation and their management before, during, and after pregnancy. In this episode, we focus on management of pregnant patients with mechanical valves and venous thromboembolism. Audio editing by CardioNerds Academy Intern, Dr. Maryam Barkhordarian. Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Cardio-Obstetrics Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls- Pregnancy and Anticoagulation Pregnancy is a hypercoagulable state. Pregnancy-associated VTE is a leading cause of maternal morbidity and mortality. The use of anticoagulation requires a balance between the risks and benefits to the mother and her fetus. The agent of choice for anticoagulation during pregnancy depends on the indication, pre-pregnancy dose of vitamin K antagonist (VKA), and the trimester of pregnancy. For instance, patients with mechanical heart valves, warfarin is generally recommended in the first trimester if the daily dose is less than 5 mg and as the first option for all patients with mechanical valves in the 2nd and 3rd trimester. Use of direct oral anticoagulants (DOACs) has not been systematically studied, they do cross the placenta and their safety remains untested. Warfarin crosses the placenta but is not found in breast milk. LMWH does not cross the placenta and is not found in breast milk. Thus, both these agents can be used by a lactating mother. Quatables – Pregnancy and Anticoagulation “[We] can’t highlight enough that good communication and documentation is vital in such situations” says Dr. Berlacher while discussing the role of a multidisciplinary team including cardiologists, obstetricians and fetal medicine physicians in taking care of a pregnant patient on anticoagulation. “What I love about cardio-obstetrics is that we really can help women in a time that is so important in their life…this is one of the most memorable times in their life..” says Dr. Berlacher when asked what makes your heart flutter about cardio-obstetrics. “Knowledge is power…not just for providers, but also for the patients” says Dr. Berlacher emphasizing the importance of clear communication between physicians and patients. Show notes – Pregnancy and Anticoagulation 1. What makes pregnancy a hypercoagulable state? Pregnancy is a hypercoagulable state associated with higher risk of thromboembolic phenomenon. The three components of Virchow’s triad: hypercoagulability, stasis, and endothelial injury are all present during pregnancy. This leads to a 5-fold increased risk of venous thromboembolism (VTE) during pregnancy that persists for 12 weeks postpartum. The risk for VTE seems to be highest in the first 6 weeks postpartum, with a higher prevalence of clot in the left lower extremity. There are additional risk factors for developing VTE in the postpartum period besides pregnancy itself, and this includes but is not limited to preeclampsia, emergent c-section, hypertension, smoking, and postpartum infection. Choosing anticoagulant therapies during pregnancy involves a fine balance between the risks and benefits to both the mother and fetus. A multidisciplinary team involving the obstetrician, cardiologist, and maternal-fetal medicine team is critical to guide anticoagulation in pregnancy. 2. What are some of the common indications for anticoagulation during pregnancy? One of the most common indications for anticoagulation in pregnancy is valvular disease, and specifically mitral valve stenosis with atrial fibrillation or a prior embolic event. Patients with a mechanical heart valve will require anticoagulation during pregnancy. Patients with a bioprosthetic valve (surgical or transcatheter) are generally continued on low dose Aspirin; in the uncommon scenario of pregnancy in the first 3-6 months following implantation of a bioprosthetic valve, the decision to pursue anticoagulation is individualized. Other indications include acute VTE, atrial fibrillation, antiphospholipid syndrome, and inherited thrombophilias that may predispose a patient to developing VTE during pregnancy. 3. For mechanical heart valves, how do anticoagulation recommendations vary based on trimester? The European Society of Cardiology has divided various valvular heart diseases into 4 classes as per the modified World Health Organization classification of maternal cardiovascular risk, and having a mechanical valve falls under Class III where the maternal cardiac event rate varies between 19-27%. Such patients should get their care at expert centers for pregnancy and cardiac disease. Anticoagulation for mechanical valve during pregnancy varies with each trimester to balance the risks and benefits. During the first trimester, the period of organogenesis, the decision of whether to continue warfarin (a potential teratogenic) depends on the dose of warfarin. If a patient has been taking </=5 mg/day of warfarin, one can either continue taking warfarin (Class IIa) or switch to LMWH/ UFH (Class IIb). However, if a patient is on >5 mg/day of warfarin, the American Heart Association (AHA) recommends stopping warfarin and using alternate agents like LMWH/UFH (Class IIa). During the second and third trimesters, it is typically advised to continue warfarin until prior to the vaginal delivery when continuous infusion of UFH should be used as the anticoagulant agent of choice. Expert multidisciplinary teams are needed not only to guide these general recommendations, but to individualize the treatment based on patient preferences and specific factors (e.g., previous prosthetic valve thromboembolic complication). For a mechanical mitral valve replacement, 2014 AHA/CC guidelines recommend a goal INR of 3.0. For a mechanical aortic valve replaceent, the goal depends on the presence or absence of risk factors. In a patient with high-risk conditions like atrial fibrillation, previous thromboembolism, LV dysfunction, hypercoagulable condition, and older-generation mechanical valve, a goal INR of 3.0 (2.5 to 3.5), similar to MVR is recommended. However, if no high-risk features exist, then an INR goal of 2.5 (2.0 to 3.0) is recommended. Additionally, no additional bridging is required in the latter group of patients if their VKA therapy is interrupted for non-cardiac procedures. With certain AVR valves and no other risk factors (e.g. ON-X), a lower INR goal may be pursued. 4. What are the major differences between Warfarin, Heparin products, and DOACs in pregnancy and lactation? Warfarin crosses the placenta and has a dose-dependent relationship with adverse fetal outcomes (e.g., miscarriage, stillbirth, embryopathy). Warfarin’s teratogenic effects are also trimester-dependent with fetal bone and cartilage abnormalities occurring in the 1st trimester and CNS abnormalities (e.g., microencephaly, spasticity, hypotonia, optic atrophy) if teratogenic levels are reached in the 2nd and 3rd trimester.  When compared with LMWH and UFH, warfarin has the least maternal risk for those with mechanical heart valves, but lowest rates of livebirths. [4] LMWH does not cross the placenta and is associated with the highest number of livebirths. However, the challenges of using LMWH include its monitoring. Weight-based LMWH should be accompanied by peak anti-Xa levels drawn 4-6 hours post-dose to achieve a goal level of 1.0-1.2 U/ml. UFH is the preferred agent of choice at the time of delivery, since this is the highest period of bleeding for a pregnant woman. It is usually stopped 4-6 hours before delivery and restarted 4-6 hours after delivery if there is no bleeding. DOACs have not been studied in pregnant patients on a large scale. And the limited data present revealed a high miscarriage rate and possible embryopathy. There use is not recommended in pregnant women. Anticoagulants such as UFH, LMWH, warfarin, fondaparinux, or danaparoid are all recommended as safe options for breastfeeding women with indication for anticoagulation. DOACs are not recommended for lactating women. 5. What are the recommendations for VTE management during pregnancy? Venous thromboembolism (VTE) complicates ∼1.2 of every 1000 deliveries. Despite these low absolute risks, pregnancy associated VTE is a leading cause of maternal morbidity and mortality. Women with VTE on chronic anticoagulation are recommended to continue anticoagulation during (and after) pregnancy. Weight-based LMWH guided by Xa levels (to achieve a goal level of 1.0-1.2 U/ml) is the preferred agent, but warfarin (daily dose ≤5 mg) is an alternative. In patients with recent pulmonary embolism (PE), postpartum heparin treatment should be restarted 6 hours after a vaginal birth and 12 hours after a caesarean delivery if no significant bleeding has occurred. There should be subsequent overlap with VKAs for at least 5 days. In the absence of significant bleeding, VKAs may be started on the second day after delivery and continued for at least 3 months, or for 6 months if PE occurred late in pregnancy. The goal INR should be between 2 and 3. Anticoagulation decisions are complex and should be determined in collaboration with a multidisciplinary cardio-obstetrics team. References Alshawabkeh L, Economy KE, Valente AM . Anticoagulation During Pregnancy: Evolving Strategies With a Focus on Mechanical Valves. J Am Coll Cardiol 2016;68:1804-1813. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. The Task Force for the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology. European Heart Journal. 2018, 39, 3165-3241. Nishimura RA, Otto CM, Bonow RO et al. 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: Executive Summary. A Report of the AMerican College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129:e521-e643. Richardson A, Shah S, Harris C, McCulloch G, Antoun P. Anticoagulation for the Pregnant Patient with a Mechanical Heart Valve, No Perfect Therapy: Review of Guidelines for Anticoagulation in the Pregnant Patient. Case Rep Cardiol. 2017;2017:3090273. Shannon M. Bates, Anita Rajasekhar, Saskia Middeldorp, Claire McLintock, Marc A. Rodger, Andra H. James, Sara R. Vazquez, Ian A. Greer, John J. Riva, Meha Bhatt, Nicole Schwab, Danielle Barrett, Andrea LaHaye, Bram Rochwerg; American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv 2018; 2 (22): 3317–3359. Lameijer H, Aalberts JJJ, van Veldhuisen DJ, Meijer K, Pieper PG. Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review. Thromb Res. 2018 Sep;169:123-127. Guest Profiles Dr. Katie Berlacher Katie Berlacher, MD, is a cardiologist and is certified in cardiovascular disease by the American Board of Internal Medicine and adult echocardiography by the National Board of Echo. She is the medical director of the Magee Women’s Heart Program, the program director of cardiovascular fellowship, and is an assistant professor of medicine at the University of Pittsburgh School of Medicine. She received her medical degree from The Ohio State University and completed her residency and fellowship at the University of Pittsburgh Medical Center. Dr. Berlacher joined the UPMC Heart and Vascular Institute in 2012. Her clinical interests include women’s heart disease, including pregnancy and heart disease risks, as well as medical education. She has published numerous articles in peer-reviewed journals and is a member of the American College of Cardiology and the American Heart Association. She lives in the city and is an avid cyclist, boxer, and hiker. Dr. Akanksha Agrawal Akanksha is a cardiology fellow at Emory University. She did her medical school from Maulana Azad Medical College, India, and Internal Medicine Residency at Einstein Medical Center, Philadelphia, where she did a year of chief residency as well. She is interested in cardio-obstetrics and advanced heart failure, and plans to pursue Advanced Heart Failure and Cardiac Transplant fellowship. CardioNerds Cardioobstetrics Production Team Natalie Stokes, MD Sonia Shah, MD Amit Goyal, MD Daniel Ambinder, MD

The CardioNerds are thrilled to launch The Cardiac Critical Care Series! The series Co-Chairs – Dr. Mark Belkin (Advanced Heart Failure FIT, U Chicago), Dr. Yoav Karpenshif (FIT, U Penn), Dr. Eunice Dugan (CardioNerds Academy Chief Fellow and FIT, Cleveland Clinic), and Dr. Karan Desai (CardioNerds Academy Editor and FIT, U Maryland) – join CardioNerds Co-Founders, Amit Goyal and Daniel Ambinder to delve into high-yield topics in critical care cardiology. We kickstart this series with one of the early pioneers and national leaders in cardiac critical care – Dr. Jason Katz, Director of Cardiovascular Critical Care and Co-Director of Mechanical Circulatory Support and the CICU at Duke University Medical Center. In this episode, we learn about Dr. Katz’s career path and what motivated him to train in Critical Care Cardiology. He shares early struggles, notable changes in this field’s nascent period, and ongoing challenges in training and practice. We discuss collaboration with other cardiac and non-cardiac specialties and their importance in comprehensive care. Furthermore, we discuss how to advance critical care research, including the Critical Care Cardiology Trials Network and future randomized controlled trials to inform our practice and develop standardized protocols. In this small but rapidly growing field, we learn there is much to discover together. Audio editing by CardioNerds Academy Intern, Hirsh Elhence. Claim free CME for enjoying this episode! Disclosures: None Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Cardiac Critical Care PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes “I think it’s really important not to be afraid of change in order to potentially succeed […] it’s okay to not entirely know what you want to do.” – Dr. Katz when sharing his non-direct career path in a novel field. “There is no greater team sport in cardiology than Cardiac Critical Care” and “I oftentimes think of the Critical Care Cardiologist as sort of the conductor that helps to orchestrate [the team]…” – Dr. Katz when discussing the importance of multidisciplinary teams and need to collaborate with other cardiac and non-cardiac sub-specialties. Many general surgical or medical residency/fellowship graduates are not comfortable caring for patients in the critical care setting. There is a need to revamp critical care training without significantly prolonging training time in order to complement and enhance our current workforce to care for complex, critically ill cardiac patients. “I don’t think there’s necessarily a one size fits all model, and I think we should be malleable or adaptable to the needs of our trainees and the needs of our patients.” – Dr. Katz when discussing training pathways in Critical Care Cardiology or combining Critical Care with other subspecialties like Interventional Cardiology or Advanced Heart Failure. Dr. Katz suggests that when choosing a Critical Care Cardiology training program: “consider geography, the flexibility of the curriculum, the overall fellowship and social experience, and the clinical setting. Everything that’s really important to choosing a cardiology fellowship is more important in my mind than if they actually have a standardized, cardiac critical care pathway.” Show notes 1. What are some recent changes in the field of Critical Care Cardiology? Compared to even just a decade ago, there is a growing interest from medical students to young faculty in pursuing a career in critical care cardiology. At the same time there is evidence that the patient demographics in our CICUs are changing, including more multi-organ dysfunction and many non-cardiac diagnoses. In a recent paper from the Critical Care Cardiology Trials Network (CCCTN), the proportion of patients with a primary diagnosis of acute coronary syndrome was only approximately 32%. Following overall trends in heart failure, a greater proportion of CICU patients have heart failure and/or heart failure phenotype cardiogenic shock requiring clinicians to be facile with the spectrum of mechanical support devices. These demographic and workforce trends are requiring cardiologists to re-think how to best meet the needs of the modern CICU. 2. What continue to be some challenges in practicing Critical Care Cardiology? CICU patients are a heterogenous group with varying baseline characteristics, comorbidities, illness severity, and treatment responses. Since distinct pathophysiologic targets are lacking, challenges exist when devising strategies to improve outcomes. Similarly, these challenges extend to developing and executing research protocols to inform management. As Dr. Katz discussed on the episode, the lack of standardization, consistent terminology, and even who belongs in the CICU, remains a barrier to devising who should staff the CICU and how we train physicians to care for CICU patients. Dr. Katz described the cardiac intensivist as akin to the conductor of an orchestra working with multiple cardiac and non-cardiac subspecialists, and other professionals such as RNs, dieticians, physical therapy, social work, chaplaincy etc.  Understanding the roles of multidisciplinary members can help inform resource utilization and allocate costs. 3. What are some challenges in Critical Care Cardiology training? There continues to be a supply-demand mismatch when it comes to the growing clinical need and the availability of trained cardiac critical care clinicians. Many surgical or medical residency/fellowship graduating trainees do not feel comfortable caring for critically ill patients. Thus, Dr. Katz advocates for outside the box thinking to find novel ways to supplement current cardiovascular training – whether it be in general fellowship, advanced heart failure or interventional training – with adequate critical care training for interested trainees. Accomplishing this goal without excessive increases in numbers of years in training – and assuring competency and exposure to aspects of critical care medicine not seen in general cardiology training – may require creating more blended pathways Furthermore, the optimal timing of when to obtain critical care training remains unclear. As few integrated options currently exist, trainees most commonly pursue critical care training after general cardiology or subspecialty cardiology fellowship training. Without integrated options, however, there is concern that trainees may not maintain their cardiac clinical skills or competency in areas such as echocardiography during dedicated critical care medicine years. 4. What about combining critical care with other cardiac-subspecialities like Interventional Cardiology or Advanced Heart Failure? There isn’t a “one size fits all” model. Training pathways should be flexible to accommodate the needs and interests of trainees. Recent opinion pieces have suggested blending Advanced Heart Failure training with Critical Care Training in a preferably 5-year pathway. Regardless of who is staffing the CICU, optimal care requires continued collaboration – not just during admission but frequent revisitation of management plans with cardiac subspecialists to direct patient care. 5. What can we learn from our cardiac intensivist colleagues in Europe? Europe has a more established training pathway for cardiac critical care with a dedicated scientific symposium, credentialing pathway, and journal. Although we have different regulatory authorities and settings for care of delivery, with colleagues in Europe having been through the process of establishing this new field, we can learn from their struggles and successes. Furthermore, there are opportunities for multinational collaboration in research, training, and education. References Il’Giovine ZJ, Menon V. The Intersection of Heart Failure and Critical Care: The Contemporary Cardiac Intensive Care Unit and the Opportunity for a Unique Training Pathway. J Card Fail. 2021 Oct;27(10):1152-1155. doi: 10.1016/j.cardfail.2021.03.014. PMID: 34625134. Katz J, Turer A, Becker R. Cardiology and the critical care crisis: a perspective. Journal of the American College of Cardiology. Published online 2007. doi:10.1016/J.JACC.2006.11.036 Bhatt AS, Berg DD, Bohula EA, et al. De Novo vs Acute-on-Chronic Presentations of Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology Trials Network Registry. J Card Fail. 2021 Oct;27(10):1073-1081. doi: 10.1016/j.cardfail.2021.08.014. PMID: 34625127; PMCID: PMC8514080. Guest Profiles Dr. Jason Katz Dr. Jason Katz is the Director of the Cardiac ICU, Mechanical Circulatory Support, and LVAD programs at Duke University. After completing his Internal Medicine residency at UT-Southwestern, he went on to complete a Cardiology Fellowship at Duke University, a Clinical Research Fellowship with the DCRI, and a finally Critical Care Fellowship at Duke. He has published over 100 articles across a range of topics within Cardiac Critical Care, including multiple reviews and statements addressing the role of, and training options for, Cardiac Intensivists. He is considered an early pioneer, and continues to be a leader, in this growing field, currently serving as the immediate past-President of the AHA Acute Cardiac Care Committee. CardioNerds Cardiac Critical Care Production Team Karan Desai, MD Dr. Mark Belkin Amit Goyal, MD Daniel Ambinder, MD

CardioNerds Tommy Das (Program Director of the CardioNerds Academy and cardiology fellow at Cleveland Clinic) and Rick Ferraro (Director of CardioNerds Journal Club and cardiology fellow at the Johns Hopkins Hospital) join Dr. Erin Michos (Associate Professor of Cardiology at the Johns Hopkins Hospital and Editor-In-Chief of the American Journal of Preventative Cardiology) for a discussion about the effect of DHA and EPA on triglycerides and why DHA/EPA combinations may have exhibited limited benefits in trials. This episode is part of the CardioNerds Lipids Series which is a comprehensive series lead by co-chairs Dr. Rick Ferraro and Dr. Tommy Das and is developed in collaboration with the American Society For Preventive Cardiology (ASPC). Relevant disclosures: None Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Lipid Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls The best intervention for heart disease is prevention! The InterHeart trial showed that 9 modifiable risk factors (dyslipidemia, smoking, hypertension, diabetes, abdominal obesity, dietary patterns, physical activity, consumption of alcohol, and psychosocial factors) predict 90% of acute myocardial infarction. So many acute events can be prevented1. Atherosclerotic vascular disease events increase across a range of triglyceride levels, even from 50-200mg/dL. So even in a relatively normal range, lower triglycerides seem to be better. Over ¼ of US adults have triglycerides over 150. While 8% of US adults take fish oil supplements, multiple meta-analyses have failed to show any benefit to the use of dietary omega-3 supplementation2. Dietary supplements these are not meant for medical use and are not studied or regulated as such! Show notes 1. What are DHA and EPA? DHA, or docosahexaenoic acid, and EPA, or eicosapentaenoic acid, are n-3 polyunsaturated fatty acids, also known as omega-3 fatty acids. These compounds have been of considerable interest for over two decades given observed association of high dietary omega-3 fatty acid intake with reduced cardiovascular events3. As both are important omega-3 fatty acids, trials on the benefits of DHA and EPA have often focused on the two compounds in combination. 2. What was the GISSI-Prevenzione Trial and why was it Important? GISSI-Prevenzione trial (Lancet 1999), was one of the earliest trials to study DHA and EPA4. In this trial, the authors evaluated the effect of omega-3 supplementation as a combination pill of DHA and EPA on cardiovascular events and death in patients with recent myocardial infarction (the last three months). Over a 3.5-year follow-up period, participants treated with DHA/EPA combination experienced a significant reduction in death, nonfatal MI, and stroke. As this was an early trial, patients were largely not on statins, as these were not supported at the time of study initiation (Only 5% were on cholesterol-lowering medications at baseline, and only 45% were on cholesterol-lowering therapy at study completion). The benefits seen in this trial may not extend to modern practice with patients on contemporary background therapy. The trial participants were also not representative of our modern patients for a variety of other reasons. 85% of participants in the trial were men. 42.2% of patients in EPA/DHA arm were current smokers, and 35.4% were prior smokers. Only 14.2% of patients had diabetes and 14.7% with BMI >30. Notably, the decrease in triglycerides in this trial was only 3%, implying that triglyceride lowering did not entirely explain the benefit in cardiovascular events seen. 3. What about the data after the GISSI-Prevensione Trial? After this positive trial for DHA/EPA in combination, subsequent trial data in support of DHA/EPA has been less robust. The Alpha Omega trial in 2010, ORIGIN in 2012, ASCEND in 2018, and VITAL in 2019 were all trials of DHA/EPA combinations versus placebo, and all exhibited no significant differences in cardiovascular events with DHA/EPA use5–8. The recent STRENGTH trial, published in 2020, also showed no reduction in cardiovascular events when taking DHA/EPA in combination (and as discussed in CardioNerds episode 136!)9. This remained the case upon sub-analysis of patients from the STRENGTH trial with the highest levels of serum EPA, who again exhibited no cardiovascular benefit. 4. Why then don’t DHA and EPA seem to work in combination? In short, we do not know. It seems that the beneficial effects of EPA – which as monotherapy has shown benefit across numerous trials (namely JELIS and REDUCE-IT) – are somehow offset by the combination with DHA, via a mitigation of anti-inflammatory processes or otherwise – this remains theoretical10,11. The EVAPORATE trial of purified EPA showed lower total plaque in participants taking EPA, suggesting a possible mechanism of effect12. 5. What About Dietary Omega-3 Supplements? 8% of US adults take fish oil supplements. Multiple meta-analyses have failed to show any benefit to the use of dietary omega-3 supplementation2. Note that the term “over the counter” is not correct when referring to these supplements! Over the counter refers to medications that are FDA regulated, just not prescription. Omega-3 supplements have minimal FDA oversight, which is perhaps another reason to avoid them. References – Triglycerides 1.     Yusuf S, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. The Lancet. 2004;364(9438):937-952. doi:10.1016/S0140-6736(04)17018-9 2.     Abbasi J. Another Nail in the Coffin for Fish Oil Supplements. JAMA. 2018;319(18):1851-1852. doi:10.1001/jama.2018.2498 3.     Bang HO, Dyerberg J, Hjørne N. The Composition of Food Consumed by Greenland Eskimos. Acta Medica Scandinavica. 1976;200(1-6):69-73. doi:10.1111/j.0954-6820.1976.tb08198.x 4.     GISSI-Prevenzione, Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. The Lancet. 1999;354(9177):447-455. doi:10.1016/S0140-6736(99)07072-5 5.     Kromhout D, Giltay EJ, Geleijnse JM. n–3 Fatty Acids and Cardiovascular Events after Myocardial Infarction. N Engl J Med. 2010;363(21):2015-2026. doi:10.1056/NEJMoa1003603 6.     The ORIGIN Trial Investigators. n–3 Fatty Acids and Cardiovascular Outcomes in Patients with Dysglycemia. N Engl J Med. 2012;367(4):309-318. doi:10.1056/NEJMoa1203859 7.     The ASCEND Study Collaborative Group. Effects of n−3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018;379(16):1540-1550. doi:10.1056/NEJMoa1804989 8.     Manson JE, Cook NR, Lee IM, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2018;380(1):33-44. doi:10.1056/NEJMoa1809944 9.     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 10.   Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. doi:10.1056/NEJMoa1812792 11.   Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. The Lancet. 2007;369(9567):1090-1098. doi:10.1016/S0140-6736(07)60527-3 12.   Budoff MJ, Bhatt DL, Kinninger A, et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. European Heart Journal. 2020;41(40):3925-3932. doi:10.1093/eurheartj/ehaa652 Guest Profiles Dr. Erin Donnelly Michos Dr. Erin Donnelly Michos is an Associate Professor of Medicine at Johns Hopkins School of Medicine, with joint appointment in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. She is the Director of Women’s Cardiovascular Health and the Associate Director of Preventive Cardiology with the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. Dr. Michos completed medical school at Northwestern University in Chicago, IL, and then completed both her Internal Medicine residency and Cardiology fellowship at the Johns Hopkins Hospital in Baltimore, MD.  She also completed her MHS in Cardiovascular Epidemiology at the Johns Hopkins Bloomberg School of Public Health. She has authored or co-authored over 300 manuscripts in peer reviewed journals and is an internationally known leader in preventive cardiology and women’s health.  CardioNerds Lipids Production Team Tommy Das, MD Dr. Rick Ferraro Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), join CardioNerds FIT Ambassador, Dr. Natasha Cuk and her co-fellows, Dr. Lily Stern, and Dr. Paul Marano from the Cedars-Sinai Cardiology Fellowship for some late afternoon smoothies on the beach. They discuss the case of a 46-year-old woman who presented with sudden cardiac arrest and was ultimately found to have a mobile intraluminal aortic thrombus adherent to a penetrating ulcer in the ascending aorta. This mobile thrombus was ultimately thought to be the cause of transient ischemia and the patient’s cardiac arrest. We discuss a differential for sudden cardiac arrest, initial management after resuscitated cardiac arrest, a differential for arterial thrombus, and review an illness script for penetrating atherosclerotic ulcers. Dr. Dominick Megna provides the provides the E-CPR for this episode. Audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship). This Case Report has been published in JACC Case Reports! Claim free CME just for enjoying this episode!  Disclosures: NoneJump to: Pearls – Notes – References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Episode Teaching https://twitter.com/LilySternMD/status/1460811173113184263?s=20 Pearls – Cardiac Arrest due to Aortic Thrombus After cardiac arrest, the initial ECG obtained after the return of spontaneous circulation can provide important information on the etiology of the arrest. The ECG can narrow our structured differential, for which one approach would be the following breakdown: acute ischemic events, structural heart disease, arrhythmogenic syndromes with no structural abnormality, and then non-cardiac causes such as drugs, toxins, trauma, metabolic arrangements The risk vs benefit of emergent angiography after sudden cardiac arrest depends on balancing the potential benefit from revascularization in an acute ischemic event vs bleeding risks and potential delays in other aspects of care, particularly given that a large percentage of mortality is related to neurologic injury from the arrest, which would not be impacted by immediate angiography. The available randomized controlled trial evidence has not demonstrated a survival or neurologic outcome benefit to immediate angiography, and the decision depends on weighing the risk/benefit for each patient. Due to high flow, a thrombus in the aorta should prompt an investigation for causes focused on the other two ‘points’ of Virchow’s triad (aside from stasis): endothelial injury and hypercoagulability. A penetrating atherosclerotic ulcer (PAU) is a deep atherosclerotic lesion where there is a focal ulceration of the elastic lamina that extends through the medial layer of the aortic wall. These lesions are most commonly associated with extensive atherosclerosis, but can also occur related to inflammatory, infectious, or traumatic causes. A PAU is a type of acute aortic syndrome and accounts for up to 8% of total acute aortic syndromes. It may present with a spectrum of symptoms, including as an incidental finding on cardiothoracic imaging or a severe chest and back pain, like an aortic dissection. While it is a subtype of aortic syndrome, PAU can also progress to become aortic dissection and rupture. Notes – Cardiac Arrest due to Aortic Thrombus 1. How might a post-ROSC ECG help determine the etiology of a sudden cardiac arrest? During our case, we discussed a systematic approach to the differential diagnosis for sudden cardiac arrest. We broke down the causes into the buckets of: Acute ischemic events Structural heart disease Arrhythmogenic syndromes with no structural heart disease Non-cardiac causes such as drugs, toxins, trauma, and metabolic arrangements The post-ROSC ECG can provide immediate information to help narrow our differential. Evidence of acute ischemia (e.g. STEMI) would provide a likely etiology and would direct immediate next steps. We can look at ECG features such as axis and conduction abnormalities to look for evidence of an underlying structural abnormality. We can also see features of arrhythmogenic syndromes without underlying structural defects, such a short or long QT or a Brugada pattern. 2. Should all patients who present with sudden cardiac arrest and for whom ROSC is achieved undergo immediate coronary angiography? In considering the timing of coronary angiography after sudden cardiac arrest, clinical experience and the available evidence indicate a tension between: The high pre-test probability for acute ischemic events as the etiology for VT/VF arrest, and possible improvement in post-ROSC outcomes from immediate coronary angiography (and revascularization). A large portion of the morbidity and mortality associated with sudden cardiac arrest is driven by neurologic injury. Immediate angiography may expose patients to additional risk (delays in targeted temperature management, bleeding risk), without benefit to a patient’s ultimate outcome due to neurologic injury. Observational data has suggested a benefit for immediate angiography after resuscitated sudden cardiac arrest, though there was concern for selection bias. Recently, there have been two randomized controlled trials that have investigated the role for immediate angiography after sudden cardiac arrest. These trials are the COACT and PEARL trials, published in 2019 and 2020, respectively. These trials each have their own limitations, though they did not demonstrate a benefit for immediate angiography on outcomes such as mortality or neurologic outcomes. There are multiple ongoing trials to provide further guidance. The most recent AHA/ACC guideline on the topic recommends immediate coronary angiography for patients with STEMI on the post-ROSC ECG (Class I), and give a Class IIa recommendation that emergency coronary angiography is reasonable for selected patients (e.g. hemodynamically or electrically unstable) with sudden cardiac arrest of suspected cardiac origin without STEMI. 3. What is an illness script for penetrating atherosclerotic ulcers? Definitions: A penetrating atherosclerotic ulcer (PAU) is a deep atherosclerotic lesion where there is a focal ulceration of the elastic lamina that extends through the medial layer of the aortic wall. PAU is a type of acute aortic syndrome (along with other disease processes such as aortic dissection, intramural hematoma). While a distinct entity, PAU can also progress and lead to intramural hematoma, dissection, and even aortic rupture. Epidemiology: PAU accounts for 8% of total acute aortic syndromes. It is typically associated with extensive atherosclerosis in older adults (age > 65) and is most commonly found in the descending thoracic aorta. It is less commonly associated with infectious, inflammatory, or traumatic etiologies. Clinical Presentation: PAU may present with a spectrum of symptoms, including as an incidental finding on cardiothoracic imaging or a severe chest and back pain, like an aortic dissection. Diagnosis: PAU can be diagnosed by multiple imaging modalities, including computed tomography angiography, magnetic resonance imaging, and transesophageal echocardiography. 4. How are penetrating aortic ulcers treated? Management of symptomatic penetrating aortic ulcers is similar to management of aortic dissection with indications for surgery including recurrent pain despite medical treatment, hemodynamic instability, aortic diameter enlargement to >55 mm, and significant periaortic hemorrhage. In asymptomatic patients who are hemodynamically stable, management is controversial–some centers support aggressive early surgical intervention while others opt for conservative medical management along with serial surveillance for aortic enlargement. References Lemkes JS, Janssens GN, van der Hoeven NW, Jewbali LSD, Dubois EA, Meuwissen M, Rijpstra TA, Bosker HA, Blans MJ, Bleeker GB, Baak R, Vlachojannis GJ, Eikemans BJW, van der Harst P, van der Horst ICC, Voskuil M, van der Heijden JJ, Beishuizen A, Stoel M, Camaro C, van der Hoeven H, Henriques JP, Vlaar APJ, Vink MA, van den Bogaard B, Heestermans TACM, de Ruijter W, Delnoij TSR, Crijns HJGM, Jessurun GAJ, Oemrawsingh PV, Gosselink MTM, Plomp K, Magro M, Elbers PWG, van de Ven PM, Oudemans-van Straaten HM and van Royen N. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. New England Journal of Medicine. 2019;380:1397-1407. Kern KB, Radsel P, Jentzer JC, Seder DB, Lee KS, Lotun K, Janardhanan R, Stub D, Hsu CH and Noc M. Randomized Pilot Clinical Trial of Early Coronary Angiography Versus No Early Coronary Angiography After Cardiac Arrest Without ST-Segment Elevation: The PEARL Study. Circulation. 2020;142:2002-2012. 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