Cardionerds: A Cardiology Podcast

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Phoo Pwint Nandar (former FIT Ambassador), Dr. Deep Shah (current FIT Ambassador), and Dr. Sugat Wagle from the Summa Health Cardiology Department for an afternoon at Cuyahoga National Valley Park. We discuss a case of a post-partum woman who presented with ventricular fibrillation arrest due to SCAD. She had ongoing advanced cardiac life support (ACLS) for nearly 60 minutes before obtaining return of spontaneous circulation. We discuss the broad differential of VF arrest, including acute coronary syndrome and spontaneous coronary artery dissection (SCAD) – among many others. We also go over the etiology and management of SCAD as well the complications. Pregnancy is a crucial stressor to the cardiovascular system and understanding its hemodynamic changes is crucial to all physicians. The E-CPR segment is provided by Dr. Grace Ayafor, Interventional cardiology faculty, Summa Health. This episode is made possible with support from Medmastery. At Medmastery you can learn some of the most important clinical skills like echo, advanced EKG, coronary angiography, PCI basics, pacemaker- and ICD troubleshooting and so much more. CardioNerds listeners can get an exclusive 15% discount on a lifetime subscription. Click HERE for details. Jump to: Case media – Case teaching – 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 Schematics & Teaching – SCAD Pearls – SCAD SCAD remains underdiagnosed. It has a wide range of clinical presentations, including chest pain, ACS, VT/VF arrest, and cardiogenic shock. Underlying etiologies of SCAD include autoimmune diseases, connective tissue disorders, fibromuscular dysplasia, external stressors, and pregnancy. There are 3 types of SCAD, and coronary angiogram is the gold standard for diagnosis. Common areas of involvement of SCAD include left anterior descending and left circumflex arteries; however, SCAD can manifest in any coronary artery as well as simultaneously in multiple coronary arteries. Left main trunk involvement is rare, more likely to be associated with the peri-partum state, and requires complex management decisions guided by a heart team approach. Most SCAD cases are benign and treated conservatively, however, some require intervention (PCI or CABG) depending on clinical severity and course. Recurrent SCAD has been reported in 10-30% of the patients and aggressive management of hypertension is recommended. Guidelines regarding SCAD management are largely based on expert consensus due to a dearth of high-quality data. Efforts to raise awareness and study this syndrome are of paramount importance. Notes – SCAD 1. What is SCAD and how does it present? Spontaneous coronary artery dissection (SCAD) is defined as an epicardial coronary dissection that is not associated with atherosclerosis or instrumentation. This occurs with hematoma formation within the tunica media,  thereby potentially compressing the arterial true lumen leading to ischemia. There are two proposed mechanisms of hematoma formation: “inside-out” and “outside-in”. The inside-out hypothesis posits that the hematoma arises from the true lumen via a dissection flap – an endothelial-intimal disruption. Conversely the outside-in hypothesis posits that the hematoma arises de novo within the media through disruption of traversing microvessels. There is a wide range of clinical presentation for SCAD varying in severity including asymptomatic / benign presentation, anginal syndromes, acute myocardial infarction, VT/VF arrest, and cardiogenic shock. Our patient presented with VF arrest and ACS. SCAD epidemiology is confounded by a lack of awareness. A high index of suspicion is warranted. Diagnosis can be missed in young or mid-life without CV risk factors who would present with atypical/mild chest pain. 2. What are the etiologies of SCAD? SCAD is associated with the peripartum state (presumed due to combination of hormonal mediated vessel wall integrity changes and hemodynamic stressors), illicit substance use, autoimmune disorders, connective tissue disorders, fibromuscular dysplasia, and vigorous external stressors. Many patients recall extreme physical or emotional stress preceding the event. Men are more likely to present in the setting of a physical stressor whereas women are more likely to report an emotional stressor. Pregnancy-associated SCAD is most common in the first week after delivery like our patient. Genetic evaluation for connective tissue disorders and aortopathy syndromes (i.e., Marfan, Loeys-Dietz, and Ehlers-Danlos) should be considered. Arterial imaging to identify significant extracoronary vascular abnormalities is recommended since there is the association of SCAD with fibromuscular dysplasia. 3. What is the gold standard to diagnose SCAD? Coronary angiography performed by an experienced interventional cardiologist is the gold standard to diagnose SCAD. The left anterior descending artery is most commonly affected, and most cases of SCAD occur in the mid-distal arteries. There are 3 angiographic variants SCAD. Type 1 is with evident with the contrast dye staining the arterial wall with multiple radiolucent lumen. Type 2 (majority of the cases including the present case) is diffuse stenosis of varying severity with subtle abrupt changes in arterial caliber (long smooth narrowing). Type 3 mimics atherosclerosis and is often difficult to differentiate from it. 4. What is the management of SCAD in acute setting? Management of SCAD depends on clinical severity. Thrombolytics should be avoided. Most cases are benign and treated conservatively with work up for secondary causes. 95% of conservatively treated patients with mild SCAD such as minimal ongoing ischemia with preserve coronary flow will heal within 30 days. More severe cases of SCAD require intervention such as PCI or CABG. Surgical approaches are preferred in left main involvement, long segments, and with diffuse coronary artery involvement like in our case. Utilizing vein grafts is preferred as most SCAD cases heal with eventual graft closure. Off note, PCI in SCAD is associated with higher complication rates and suboptimal outcomes, including risk of iatrogenic dissection or propagation of hematoma. 5. What is the management of SCAD in pregnant patient? The management strategy of SCAD during pregnancy is similar to that in the nonpregnant state, with additional considerations to optimize maternal and fetal outcomes. After 20 weeks gestation, recommend left lateral recumbent positioning whenever possible to reduce aortocaval compression and optimize venous return. If necessary, consider maternal stabilization and optimization of cardiac status followed by planned delivery under controlled conditions. For more, enjoy Episode #167 – Cardiac Interventions During Pregnancy with Dr. Michael Luna. 5. What is the prognosis of SCAD and long-term management?   Recurrent SCAD has been reported in 10-30% of patients. Post-SCAD chest pain is common and may persist for many months. Due to iatrogenic risk from invasive angiography, serial electrocardiography and biomarker assessment, and noninvasive cardiac computed tomography angiography should be considered. Standard heart failure medications are indicated for left ventricular dysfunction, and hypertension should be treated. 6. How to prevent recurrent SCAD? The factors associated with recurrence remain poorly understood. After SCAD, further pregnancy should perhaps be discouraged and contraception should be discussed. Women who strongly desire pregnancy should receive thorough preconception counseling. References Macaya, F., Salinas, P., Gonzalo, N., Fernández-Ortiz, A., Macaya, C., & Escaned, J. (2018). Spontaneous coronary artery dissection: contemporary aspects of diagnosis and patient management. Open Heart, 5(2), e000884. Hayes, S. N., Kim, E. S. H., Saw, J., Adlam, D., Arslanian-Engoren, C., Economy, K. E., Ganesh, S. K., Gulati, R., Lindsay, M. E., Mieres, J. H., Naderi, S., Shah, S., Thaler, D. E., Tweet, M. S., & Wood, M. J. (2018). Spontaneous Coronary Artery Dissection: Current State of the Science: A Scientific Statement From the American Heart Association. Circulation, 137(19). McGrath-Cadell, L., McKenzie, P., Emmanuel, S., Muller, D. W. M., Graham, R. M., & Holloway, C. J. (2016). Outcomes of patients with spontaneous coronary artery dissection. Open Heart, 3(2), e000491. Alonso-Fernández-Gatta, M., Uribarri, A., Diego-Nieto, A., & Sánchez, P. L. (2017). Progressive spontaneous coronary artery dissection secondary to fibromuscular dysplasia requiring mechanical circulatory support. Journal of Cardiology Cases, 16(6), 216–218. Cepas-Guillén, P. L., Flores-Umanzor, E. J., Sabate, M., & Masotti, M. (2019). Multivessel spontaneous coronary artery dissection involving the left main coronary artery: a case report. European Heart Journal – Case Reports, 3(1). Tweet, M. S., Eleid, M. F., Best, P. J. M., Lennon, R. J., Lerman, A., Rihal, C. S., Holmes, D. R., Jr, Hayes, S. N., & Gulati, R. (2014). Spontaneous Coronary Artery Dissection. Circulation: Cardiovascular Interventions, 7(6), 777–786. Hayes SN, Tweet MS, Adlam D, et al. Spontaneous Coronary Artery Dissection: JACC State-of-the-Art Review. J Am Coll Cardiol 2020;76:961-984.

CardioNerds (Daniel Ambinder), ACHD series co-chairs,  Dr. Josh Saef (ACHD fellow, University of Pennsylvania) Dr. Daniel Clark (ACHD fellow, Vanderbilt University), and ACHD FIT lead Dr. Jon Kochav (Columbia University) join Dr. Eric Krieger (Director of the Seattle Adult Congenital Heart Service and the ACHD Fellowship, University of Washington) to discuss multimodality imaging in congenital heart disease. Audio editing by CardioNerds Academy Intern, Dr. Maryam Barkhordarian. Special introduction to CardioNerds Clinical Trialist Dr. Shiva Patlolla (Baylor University Medical Center). In this episode we discuss the strengths and weaknesses of the imaging modalities most commonly utilized in the diagnosis and surveillance of patients with ACHD.  Specifically, we discuss transthoracic and transesophageal echocardiography, cardiac MRI and cardiac CT. The principles learned are then applied to the evaluation of two patient cases – a patient status post tetralogy of Fallot repair with a transannular patch, and a patient presenting with right ventricular enlargement of undetermined etiology. The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark. The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more Disclosures: None Pearls • Notes • References • Guest Profiles • Production Team CardioNerds Adult Congenital Heart Disease PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls – Cardiovascular Multimodality Imaging in Congenital Heart Disease Transthoracic echocardiography (TTE) is the first line diagnostic test for the diagnosis and surveillance of congenital heart disease due to widespread availability, near absent contraindications, and ability to perform near comprehensive structural, functional, and hemodynamic assessments in patients for whom imaging windows allow visualization of anatomic areas of interest. Transesophageal echocardiography (TEE) use in ACHD patients is primarily focused on similar indications as in acquired cardiovascular disease patients: the assessment of endocarditis, valvular regurgitation/stenosis severity and mechanism, assessment of interatrial communications in the context of stroke, evaluation for left atrial appendage thrombus, and for intraprocedural guidance. When CT or MRI are unavailable or contraindicated, TEE can also be used when transthoracic imaging windows are poor, or when posterior structures (e.g. sinus venosus, atrial baffle) need to be better evaluated. Cardiac MRI (CMR) with MR angiography imaging is unencumbered by imaging planes or body habitus and can provide comprehensive high resolution structural and functional imaging of most cardiac and extracardiac structures. Additional key advantages over echocardiography are ability to reproducibly quantify chamber volumes, flow through a region of interest (helpful for quantifying regurgitation or shunt fraction), assess for focal fibrosis via late gadolinium enhancement imaging, and assess the right heart. Cardiac CT has superior spatial resolution in a 3D field of view which makes it useful for clarifying anatomic relationships between structures, visualizing small vessels such as coronary arteries or collateral vessels, and assessing patency of larger vessels (e.g branch pulmonary arteries) through metallic stents which may obscure MR imaging. Downsides relative to CMR include requirement of nephrotoxic contrast for imaging of intracardiac/intravascular structures, and while gated images can be obtained throughout the cardiac cycle similarly to CMR, this is particularly costly from an ionizing radiation standpoint. When working up an unknown congenital lesion, it is critical to communicate the differential diagnosis when ordering a test so that the imager can protocol the study accordingly. Not all echocardiograms, CT or MRI scans are the same. Show notes – Cardiovascular Multimodality Imaging in Congenital Heart Disease What are the key strengths and weaknesses of transthoracic echocardiography? STRENGTHS: (1) “Most important ability is availability”: Transthoracic echocardiography is the first line imaging modality in the assessment of patients with congenital heart disease because it is widely available at significantly lower cost with no contraindications or risks to the patient. (2) Versatility: A wide array of echo approaches can be employed to provide comprehensive structural and physiological data. 2D echo techniques are most useful for visual assessment of cardiac structural abnormalities. Color doppler provides qualitative data regarding flow, and spectral doppler (inclusive of tissue doppler imaging) provides quantitative data defining intracardiac hemodynamics. 3D echo can be applied to optimize imaging planes for valve area planimetry and quantify chamber volumes as well as global contractile function. Strain imaging using 2D speckle tracking techniques can be employed to evaluate regional contractility. (3) High temporal resolution: High temporal resolution makes echocardiography a superior modality for imaging fast-moving structures (e.g., valvular vegetations or intracardiac masses). WEAKNESSES: (1) “You can’t study what you can’t see”: Suboptimal ultrasound penetration can limit transthoracic imaging quality in patients with large body habitus, or patients in the post-operative state. Furthermore, imaging planes are limited by sonographic windows – many anatomic cardiac (e.g., sinus venosus and coronary sinus defects, anomalous coronary arteries) and extracardiac (e.g., aortic dilation/coarctation, anomalous venous return) abnormalities are often incompletely evaluated by echocardiography in adult patients. This is a major limitation as many ACHD conditions are associated with aortopathy and anomalous pulmonary or systemic venous return which may necessitate dedicated cross-sectional imaging. Finally, right ventricular imaging is limited by near field artifact and complex chamber geometry; and similarly anterior structures such as right ventricular to pulmonary arterial conduits are poorly evaluated with transthoracic echocardiography. What differentiates a congenital echocardiogram from a standard adult protocol? Congenital echocardiograms obtain more comprehensive anatomic evaluation to visualize structural anomalies that might not be evident in standard imaging planes. Most congenital echo protocols begin with a subcostal short axis and long axis sweep to determine segmental anatomy, visceral and atrial situs, cardiac position, cardiac looping, and arterial situs. Additional views are attempted from the suprasternal position to better characterize major venous and arterial connections and anatomy (bidirectional Glenn, etc.). Sweeps are often obtained between views within the same window to clarify the relationships between anatomic structures and identify abnormalities (e.g. inter-chamber connections) not apparent in the standard imaging planes. What is the role of transesophageal echocardiography in adult congenital cardiology imaging? In adult patients with acquired cardiovascular disease, transesophageal echocardiography (TEE) is most commonly employed for the assessment of endocarditis, valvular regurgitation/stenosis severity and mechanism, assessment of interatrial communications in the context of stroke, evaluation for left atrial appendage thrombus, and for intraprocedural guidance. Each of these indications are also commonly encountered in an ACHD population. In congenital cardiology, improved spatial resolution of posterior heart structures can similarly be leveraged to image pathology not well visualized by a transthoracic approach such as for identifying sinus venosus defects, characterizing secundum atrial septal defects to determine feasibility of percutaneous closure, or for assessment of baffle leak on Fontan or atrial switch D-TGA patients. Additionally, TEE increasingly plays a critical role in the perioperative setting (e.g., examining physiology pre- and post-bypass) and for monitoring and guidance of percutaneous interventions in the cardiac catheterization lab. What are the key strengths and weaknesses of Cardiac MRI? STRENGTHS: (1) Unencumbered imaging planes: Unlike echocardiography, for which views are limited by echocardiographic windows, cardiac MRI technicians can prescribe unlimited imaging planes for a more complete coverage of both intracardiac and extracardiac anatomy – particularly with addition of MR angiography. This allows for improved assessment of anterior structures (e.g., the RV, RV-PA conduits), posterior structures (e.g., atrial baffles, sinus venosus or coronary sinus defects), and extracardiac anomalies (e.g., anomalous venous return, aortopathies, pulmonary arterial stenoses), which are usually poorly imaged by echocardiography in adults. Additionally, imaging is generally unaffected by body habitus, and may be used as the primary imaging modality for patients with poor transthoracic windows. (2) Reproducible volumetric quantification: Cardiac MRI is the gold standard for chamber volume assessment. Chamber volumes are obtained from endocardial contouring of Cine-CMR short axis stacks, allowing for measurements that are independent of geometric assumptions – particularly useful for right ventricular or single ventricle assessments. High inter- and intra-reader reproducibility makes CMR an ideal tool for surveillance of chamber size and function over time, and for assessing response to interventions. (3) Reproducible flow quantification: Phase contrast pulse sequences are utilized to quantify flow in any imaging plane though a region of interest (e.g., aortic/pulmonary arteries, systemic/pulmonary venous return, branch arteries). This tool can be used in ACHD patients for non-invasive measurement of Qp (pulmonary circuit flow) and Qs (systemic circuit flow) to determine shunt fraction (Qp/Qs), or for quantification of regurgitant volumes in valvular insufficiency (e.g., quantification of pulmonary regurgitation). Measurement of flow velocity across a stenosis can be used to estimate trans-stenotic pressure gradients analogous to echocardiographic spectral doppler – however gradients may be underestimated due to decreased temporal resolution of CMR imaging (peak velocity through region of interest can be missed) or imaging plane not being at the vena contracta (a higher velocity may be obtained at a higher or lower imaging plane). (4) Tissue characterization: Late gadolinium enhancement CMR can be utilized to assess for myocardial fibrosis – which can be used to identify myocardial infarction in patients with coronary abnormalities, and risk-stratify arrhythmic risk in various conditions (e.g., Tetralogy of Fallot, systemic right ventricle). (5) 3D evaluation: 3D images can be obtained, allowing for assessment of cardiac structures and their anatomic relations in all planes post image acquisition. Images can be used to produce 3D-printed heart models for surgical planning. WEAKNESSES: (1) Not everyone can get an MRI: CMR is contraindicated in patients with ferrous metallic implants. Guidelines now support the use of CMR with both MRI-conditional and legacy cardiac implantable electrical devices – but the need for careful device reprograming and patient monitoring may present logistical hurdles. The risk of nephrogenic systemic fibrosis with the use of gadolinium-based contrast agents in patients with advanced renal disease seems to have been largely mitigated with increased use of cyclic gadolinium-based contrast agents. Moreover, contrast is not required for most of the imaging indications in congenital heart disease. Claustrophobia may be a barrier to a complete CMR study in some patients, as may be intolerance of prescribed breath holds and/or prolonged reclined positioning for patients with heart failure and pulmonary edema. (2) Reduced image quality in irregular heartbeats: Irregular heart rhythms can impact gating and degrade image quality – a limitation that can be partially mitigated with prospective gating techniques. (3) The study is only as good as the protocol: MRI technicians prescribe various pulse sequences in specific imaging planes in accordance with the ordered protocol. If there is miscommunication with respect to the clinical question being asked, or the technician is not experienced in imaging patients with congenital heart disease, targeted imaging may not be performed rendering the test nondiagnostic (e.g., a cardiac MRI without MR angiography may miss an anomalous pulmonary vein in a patient with dilated right ventricle). Is Cardiac CT just Cardiac MRI with iodinated contrast and ionizing radiation? Cardiac CT has a number of distinct advantages over cardiac MRI – including rapid image acquisition time, greater spatial resolution in a 3-dimensional field of view useful for evaluation of small structures (coronaries, AV malformations, collaterals) and for clarifying anatomic relationships between structures (ideal modality for 3D printing), and ability to be used in patients with cardiac implanted electrical devices without logistic headaches. Gated acquisitions throughout the cardiac cycle can be used to assess ventricular function, although temporal resolution is lesser compared to cardiac MRI and radiation dose for such acquisitions can be substantial. CT angiography also has advantages over MRI in patients for whom prior implanted devices (e.g., stents, coils) obscure the imaging field of interest due to magnetic susceptibility artifact. Ultimately, in young patients who will need multiple imaging studies over the course of their lives, the cumulative ionizing radiation dose associated with cardiac CT is a significant disadvantage. Unlike Echo or CMR, CT imaging does not provide any information on blood flow or cardiac hemodynamics. Lesion-specific examples: In these notes, and in the episode, we present two common clinical scenarios in adult congenital heart disease to highlight the importance of a multimodality imaging approach for the diagnosis and surveillance of patients with adult congenital heart disease – (1) assessment of patients with tetralogy of Fallot, and (2) evaluation of patients with right-sided dilatation for shunt. The optimal care of these complex patients often requires appropriate utilization of multiple modalities to leverage the strengths of each. Lesion TTE TEE Cardiac MRI Cardiac CT Tetralogy of Fallot (1) Routine assessment of RV and LV size and function (2) Routine semiquantitative assessment of pulmonic valve regurgitation (3) Evaluation of PVR/conduit gradients, and RV pressure via tricuspid regurgitation gradient (4) Evaluation of proximal aortic dilation, proximal pulmonary artery branch stenosis (5) Identification of residual intracardiac shunts (1) Intraoperative management (pre- and post- bypass imaging). (2) Comprehensive echocardiographic evaluation when transthoracic windows are limited, and advanced imaging modalities are unavailable.   (1) Quantitative evaluation of PR severity (phase contrast MRI) when echo-derived severity is inconclusive (2) Serial quantitative assessment of RV volume and ejection fraction to evaluate indications for PVR or conduit replacement in patients with pulmonary insufficiency. (3) MR angiography of aorta and pulmonary artery/branches to assess for dilation or stenosis. (4) Quantitative flow assessment of differential pulmonary arterial blood flow in the setting of branch PA stenosis (phase contrast MRI). (5) Late gadolinium enhancement imaging to assess for RV fibrosis in arrhythmia risk stratification.       (1) Can be used for quantitative RV volume and ejection fraction assessment when CMR is contraindicated at expense of ionizing radiation. (2) Detailed evaluation of aortic and pulmonary arterial anatomy. (3) Detailed evaluation of coronary artery anatomy (e.g., relation of coronary artery to RV to PPA conduit prior to percutaneous valve implantation) (4) Evaluation of aortopulmonary collaterals.    Suspected simple pre-tricuspid shunt lesion (i.e. isolated RV dilatation) (1) Evaluation of right ventricular size and function. (2) Evaluation of left-sided heart disease as a cause of right-heart disease. (3) Estimation of RV/PA pressure via tricuspid regurgitation gradient to evaluate for suitability of shunt closure (e.g. PA pressure less than 50% of systemic pressure), or alternate explanations of RV dilatation (e.g. primary pulmonary hypertension). (4) Evaluation of the interatrial septum for dropout on 2D images and interatrial flow on color doppler imaging consistent with atrial septal defect (best for visualizing primum and secundum defects). (5) Evaluation of IVC flow for evidence of a scimitar vein (anomalous venous return from R pulmonary veins). (6) L arm bubble study to assess for evidence of coronary sinus defect in patient with dilated and possibly unroofed coronary sinus. (1) Evaluation for sinus venosus defect in patients with suspected L–>R shunt but no ASD seen on TTE. (2) Evaluation of SVC flow for evidence of partial anomalous venous return from R upper or middle pulmonary veins). (3) Anatomic evaluation of secundum-type defects for candidacy for percutaneous therapy (measurement of defect rim size). (4) Intraprocedural guidance for percutaneous ASD closure. (1) Quantitative assessment of RV volume and ejection fraction. (2) Non-invasive measurement of shunt fraction (Qp:Qs >1.5 suggests hemodynamically significant  shunt) (3) Evaluation for sinus venosus defect in patients with suspected L–>R shunt but no ASD seen on TTE. (4) MR angiography to assess for evidence of anomalous pulmonary venous return (R upper/middle pulmonary veins to SVC, R lower vein or complete R venous drainage to IVC [Scimatar], L venous drainage to innominate [vertical vein] or L venous drainage to coronary sinus).   (1) CTA to assess for evidence of anomalous pulmonary venous return in patients with contraindications to MR angiography.   References 1.  Di Salvo G, Miller O, Babu Narayan S, et al. Imaging the adult with congenital heart disease: a multimodality imaging approach-position paper from the EACVI. Eur Heart J Cardiovasc Imaging. 2018;19(10):1077-1098. 2. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(14):e637-e697. 3. Sachdeva R, Valente AM, Armstrong AK, et al. ACC/AHA/ASE/HRS/ISACHD/SCAI/SCCT/SCMR/SOPE 2020 Appropriate Use Criteria for Multimodality Imaging During the Follow-Up Care of Patients With Congenital Heart Disease: A Report of the American College of Cardiology Solution Set Oversight Committee and Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Pediatric Echocardiography. J Am Coll Cardiol. 2020;75(6):657-703. Meet Our Collaborators! Adult Congenital Heart AssociationFounded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers CHiP Network The CHiP network is a non-profit organization aiming to connect congenital heart professionals around the world. Visit their website (thechipnetwork.org) and become a member to access free high-quality educational material, upcoming news and events, and the fantastic monthly Journal Watch, keeping you up to date with congenital scientific releases. Visit their website (https://thechipnetwork.org/) for more information. Heart UniversityHeart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of educational material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practicing provider. The site provides free content to a global audience in two broad domains: 1. A comprehensive curriculum of training modules and associated testing for trainees. 2. A curated library of conference and grand rounds recordings for continuing medical education. Learn more at www.heartuniversity.org/ Guest Profiles Dr. Eric Krieger Dr. Eric Krieger is the Associate Director of the University of Washington’s Adult Congenital Heart Disease Program – where he directs the ACHD training program. Dr. Krieger is a multimodality imager – with expertise in applications of cardiac MRI in congenital heart disease. Dr. Jon Kochav Dr. Jon Kochav is an ACHD fellow at Columbia University Medical center. During his general fellowship he spent two research years at the Cardiac MRI lab at Weill Cornell Medical Center. CardioNerds Adult Congenital Heart Disease Production Team Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder), join Dr. Kara Denby (Interventional cardiology fellow, Cleveland Clinic), Dr. Tony Pastor (ACHD fellow, Harvard Medical School), Dr. Katie Berlacher (Cardiology program director, UPMC), and Dr. Stephen Cook (ACHD cardiologist, Indiana University) to discuss empowering the LGBTQIA+ community of cardiovascular patients & professionals and more in this installment of the Narratives in Cardiology Series. This episode features the Indiana ACC Chapter. Episode introduction and audio editing by CardioNerds Academy Intern, Pace Wetstein. This discussion was inspired by this perspective piece on ACC.org titled: Finding Our Voices: Building an LGBTQIA+ Community Within Cardiology. To learn more about diversity and equity among the LGBTQIA+ population, check out this webinar organized by the ACC. 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 • 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! Tweetorial – Empowering the LGBTQIA+ Community of Cardiovascular Patients & Professionals https://twitter.com/Gurleen_Kaur96/status/1526334939830034432?s=20&t=wMk75ORn1_KJtMTOY1IAdw Video version – Empowering the LGBTQIA+ Community of Cardiovascular Patients & Professionals Coming soon Production Team Dr. Gurleen Kaur Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Sonu Abraham (Cardiology fellow, Lahey Hospital and Medical Center), Dr. Amitoj Singh (Internal Medicine Resident, Lahey Hospital and Medical Center), Dr. Ahmed Ghoneem (Internal Medicine Resident, Lahey Hospital and Medical Center, CardioNerds Academy Chief) and Dr. Aanika Balaji (Internal Medicine Resident, Johns Hopkins) for a scrumptious meal on the Boston Harbor as they discuss a case of a young woman with metastatic melanoma on immune checkpoint inhibitors presenting with dyspnea. The presentation, risk factors, work up and management of patients with immune checkpoint inhibitor induced myocarditis are described. The E-CPR segment is provided by Dr. Sarju Ganatra, the founding director of the cardio-oncology program at Lahey Clinic.  CardioNerds Clinical Trialist Dr. Carrie Mahurin (University of Vermont Medical Center) is introduced at the beginning of the episode. A 41-year-old woman presented with mild dyspnea on exertion and non-productive cough. She had a history of Hashimoto thyroiditis, nodular thyroid s/p resection on levothyroxine, and metastatic melanoma on immune checkpoint inhibitor therapy with ipilimumab and nivolumab. She also had a history of obesity and underwent gastric bypass surgery several years prior. Though she lost weight after the surgery, she regained a significant amount and was 244 lbs with a BMI of 42. Her exam findings were remarkable for tachycardia, bilateral pulmonary rales, elevated JVP, and symmetric pedal edema. Investigations revealed a mild troponin elevation, non-specific EKG changes, and TTE with severely reduced left ventricular function (EF 15%) and a low GLS. Cardiac MRI showed patchy delayed myocardial enhancement in a non-ischemic distribution with marked global hypokinesis and EF of 11%. Endomyocardial biopsy confirmed the diagnosis of immune checkpoint inhibitor (ICI) associated myocarditis. The ICI therapy was discontinued and she was treated with high dose intravenous corticosteroids followed by a prolonged oral steroid taper with clinical improvement and complete recovery of left ventricular function. Jump to: Case media – Case teaching – 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 – immune checkpoint inhibitor myocarditis Episode Schematics & Teaching CardioNerds Myocarditis, updated 1.20.21 Pearls – immune checkpoint inhibitor myocarditis ICI-associated myocarditis has a high mortality rate necessitating a high degree of clinical suspicion. When in doubt, check it out! The initial 4 diagnostic pillars include EKG, troponin, BNP and TTE. Cardiac MRI and endomyocardial biopsy help to confirm the diagnosis. Left ventricular function is normal in 50% of these patients with ICI-associated myocarditis, so the ejection fraction is not a sensitive test for ruling this out. Endomyocardial biopsy should be considered in patients with a high clinical suspicion but negative or ambiguous non-invasive imaging. Early initiation of corticosteroids within 24 hours of presentation is associated with better outcomes. ICIs should be discontinued indefinitely in those with Grade 3 or 4 disease. Notes – immune checkpoint inhibitor myocarditis 1. Immune checkpoint inhibitors – What are they and why should we as cardiologists know about them? Immune checkpoint inhibitors (ICI) boost the host immune response against tumor cells by inhibiting the intrinsic brakes of the immune response. There are currently 7 FDA approved drugs in this group: one CTLA-4-blocking antibody called ipilimumab; three PD-1-blocking antibodies [nivolumab, pembrolizumab, and cemiplimab]; and three PD-L1-blocking antibodies [atezolizumab, avelumab, and durvalumab]. Like a car, T-cells have an ignition switch, gas pedals, and brakes. T-cells become activated when receptors on the surface of the T-cell bind to an antigen on the surface of the invading cells like cancer cells. Think of the T-cell receptor as the ignition switch and the antigen as the key. Antigen presenting cells patrol the body and pick up evidence of foreign antigens like cancer which they present to T-cells in the lymph nodes via the T-cell receptor. Like gas pedals, there are co-stimulatory signals like CD 28 which interact with proteins on the antigen presenting cells. With these “gas pedal” stimuli, T-cells get activated, multiply, and hunt for the cancer and finally kill the cancer cells. The T-cells also have “breaks” or “checkpoints” to down-regulate the immune response. The Cytotoxic T-lymphocyte antigen 4, also called the CTLA-4, acts to slow down the activation of T-cells. Further down the line, there is another checkpoint called the Programmed cell death 1 or PD-1. PD-1 is a molecule on the surface of T-cells which acts as another set of brakes. When a T cell with PD-1 on its surface interacts with another cell which has a PD-1 ligand (PD-L1), the T-cell activity is down-regulated. Many cancer cells overexpress PD-L1 to fight back against the T cells, by putting a “brake” on their immune response. By removing these brakes, we can augment the T-cells’ immune response against cancer cells. But if the T-cells mount an exaggerated response against normal host cells, then an autoimmune process ensues leading to “immune-related adverse events” (irAEs) like ICI-associated myocarditis. 2. Who are at risk of developing ICI-associated myocarditis? Anti-CTLA 4 therapy is associated with a higher prevalence of cardiotoxicity than the PD-1 and PD-L1 inhibitors. Combination therapy (i.e., when 2 or more ICIs are given together) increase the risk of irAEs. Preexisting diabetes, obesity, and autoimmune disease have been found to be independent risk factors. An association of preexisting cardiovascular risk factors like hypertension and smoking with the development of ICI-induced myocarditis has been suggested. 3. What are the prevalence and prognosis of ICI-associated myocarditis? Immune checkpoint inhibitors have various forms of cardiotoxicities, but ICI-associated myocarditis is the most feared complication. The overall prevalence is 1.2% to 2.4% when using combination ICI therapy. However, the estimated rate of mortality in ICI associated myocarditis is 38 to 46%. Approximately 50% of these patients with myocarditis may develop heart failure, cardiogenic shock, complete heart block, cardiac arrest, and ventricular arrhythmias. 4. What is the differential diagnose for ICI-associated myocarditis? The differential diagnoses are acute coronary syndrome, stress cardiomyopathy, other forms of myocarditis, pericarditis, pneumonitis, viral myocarditis, endocrinopathies, cardiac sarcoidosis and other causes of cardiomyopathy and heart failure including prior cardiotoxic therapy. 5. What are the initial investigations to be done for ICI-associated myocarditis? EKG, troponin, BNP, and TTE (as needed) are the basic 4 pillars of testing in patients with suspected ICI induced myocarditis. Nearly all patients with myocarditis have an abnormal EKG. These are however non-specific findings like sinus tachycardia, QRS or QT prolongation, conduction abnormalities, diffuse T-wave inversion, abnormal Q waves, atrial or ventricular arrhythmias, local or diffuse ST elevation. Troponins are elevated in most cases, up to 94% in one study. The implications of the level of troponin elevation are not completely clear but there is data that suggests that higher levels of troponin elevation are associated with worse cardiovascular outcomes. BNP can be elevated if the patient is in heart failure or volume overloaded. However, it lacks sensitivity and specificity for ICI associated myocarditis and is not always helpful. Even patients with fulminant myocarditis can present with a normal left ventricular function. Around 50% of patients with ICI induced myocarditis have been found to have a normal LV function. Also, among those who had major adverse cardiac events, 38% had a normal EF. 6. How do you grade severity? The American Society of Clinical Oncology broadly categorized the intensity of disease into 4 groups: G1 – Mildly abnormal screening tests and no symptoms G2 – Abnormal screening tests with mild symptoms G3 – Moderately abnormal screening tests (arrhythmia, cardiac biomarker > upper limits of normal and significant echocardiographic findings) and symptoms with mild activity. G4 – Moderate to severe decompensation, hemodynamic instability, cardiac biomarker > 3 upper limit of normal, requiring intravenous medications or interventions. To summarize, G1 and G2 are considered stable and minimally symptomatic and G3 and G4 are very symptomatic or unstable patients and will need to be admitted.                     7. What are the treatment options? Prompt initiation of immunosuppressive therapy is critical for these patients. The first line agents are corticosteroids. Start with high dose corticosteroids within 24 hours of presentation. Typically, we start with intravenous methylprednisolone 1000 mg daily for 3 days, followed by oral prednisone 1 mg/kg/day. The steroids should then be tapered slowly over at least 4–6 weeks only after resolution of symptoms, normalization of LVEF or stabilization of arrhythmias. If unresponsive to steroids, tacrolimus, mycophenolate mofetil, anti-thymocyte globulin, iv gamma globulin and plasmapheresis are alternative therapies. 8. Is it safe to restart ICIs after treatment? The current recommendation is a definite discontinuation of ICI in case of grade 3 (severe) or life threatening (grade 4) immune related adverse events. May consider re-challenge in those with milder disease and complete cardiac recovery – individualized and multidisciplinary team approach. References Patel RP, Parikh R, Gunturu KS, et al. Cardiotoxicity of Immune Checkpoint Inhibitors. Curr Oncol Rep. 2021;23(7):79. Published 2021 May 3. doi:10.1007/s11912-021-01070-6 Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018;71(16):1755-1764. doi:10.1016/j.jacc.2018.02.037 Ganatra S, Neilan TG. Immune checkpoint inhibitor-associated myocarditis. Oncologist. 2018;23(8):879–86. https://doi.org/10. 1634/theoncologist.2018-0130 Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, et al. Major adverse cardiovascular events and the timing and dose of corticosteroids in immune checkpoint inhibitorassociated myocarditis. Circulation. 2020;141(24):2031–4. https:// doi.org/10.1161/CIRCULATIONAHA.119.044703 Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714-1768. doi:10.1200/JCO.2017.77.6385

The CardioNerds Academy Class of 2021 graduation ceremony kicked off the inaugural Sanjay V Desai Lecture: Growth Mindset, Power of Yet, & Pursuit of Mastery. Join us as Dr. Tommy Das (CardioNerds Academy Program Director), and Dr. Saman Nematollahi (CardioNerds Academy Director of Research) discuss Growth Mindset with Dr. Keri Shafer and Dr. David Hirsh. Terrific acting by Dr. Patrick Zakka, Dr. Teodora Donisan, Dr. Ahmed Ghoneem, and Dr. Jessie Holtzman. Dr. Sanjay V Desai serves as the Chief Academic Officer, The American Medical Association and is the former Program Director of the Osler Medical Residency at The Johns Hopkins Hospital. Dr. Keri Shafer is an adult congenital heart disease specialist at Boston Children’s Hospital, and an assistant professor of pediatrics within Harvard Medical School. She completed internal medicine residency at Beth Israel Deaconess Medical Center, before completing cardiology fellowship at UT Southwestern and Adult Congenital and Pulmonary Hypertension subspecialty training at Boston Children’s and BWH.    Dr. David Hirsh is an associate professor of Medicine within Harvard Medical School, as well as the director of the HMS Academy fellowship in medical education and the associate dean of undergraduate medical education. Relevant disclosures: None CardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

CardioNerds, Amit Goyal, Dr. Tommy Das (Program Director of the CardioNerds Academy and Cardiology fellow at Cleveland Clinic), Dr. Rick Ferraro (Director of CardioNerds Journal Club and Cardiology fellow at the Johns Hopkins Hospital), Dr. Patrick Zakka (CardioNerds Academy Chief fellow of House Jones and Cardiology fellow at UCLA) discuss omega-3 fatty acids & the battle of the oils with Dr. Pam Taub, Director of Step Family Foundation Cardiovascular Rehabilitation and Wellness Center and Professor of Medicine at UC San Diego. Learn all about the different types of omega-3 fatty acids and the differences between prescription omega-3 fatty acids and dietary supplement fish oils. Audio editing by CardioNerds Academy Intern, Shivani Reddy. 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 Cardiovascular Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls – Omega-3 Fatty Acids & The Battle Of The Oils Coming soon! Show notes – Omega-3 Fatty Acids & The Battle Of The Oils Coming soon! References – Omega-3 Fatty Acids & The Battle Of The Oils Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Sep 10;140(11):e649-e650] [published correction appears in Circulation. 2020 Jan 28;141(4):e60] [published correction appears in Circulation. 2020 Apr 21;141(16):e774]. Grundy SM, Stone NJ, Bailey AL, et al. 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 [published correction appears in Circulation. 2019 Jun 18;139(25):e1182-e1186]. Circulation. 2019;139(25):e1082-e1143. Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk [published correction appears in Atherosclerosis. 2020 Jan;292:160-162] [published correction appears in Atherosclerosis. 2020 Feb;294:80-82]. Atherosclerosis. 2019;290:140-205. Bhatt D, Steg P, Miller M et al., 2019. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), pp.11–22. Budoff M, Bhatt D, 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. Eur Heart J. 2020;41(40):3925-3932. Nicholls S, Lincoff A, 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. Guest Profiles Dr. Pam Taub Dr. Pam Taub, Professor of Medicine, is the founding director of the StepFamily Foundation Cardiac Rehabilitation and Wellness Center at the University of California, San Diego. Dr. Taub is a leader in preventive cardiology and has authored over one hundred publications, abstracts and book chapters. Dr. Taub is a leader in multiple professional societies, including board membership for the American Society of Preventive Cardiology. Dr. Patrick Zakka Dr. Patrick Zakka completed his medical school at the American University of Beirut in Lebanon, followed by internal medicine residency and a chief resident year at Emory University. He is currently a first year cardiology fellow at UCLA and graduated as a CardioNerds fellow in House Taussig and is now the Chief Fellow of House Jones. CardioNerds Lipids Production Team Tommy Das, MD Dr. Rick Ferraro Amit Goyal, MD Daniel Ambinder, MD

In this episode we discuss cardiogenic shock due to valvular heart disease. Join Dr. Pranoti Hiremath (Interventional cardiology fellow, Johns Hopkins), Dr. Karan Desai (CN Critical Care Series Co-Chair, Cardiology fellow, University of Maryland), Dr. Yoav Karpenshif (CN Critical Care Series Co-Chair, Chief cardiology fellow, University of Pennsylvania), and Amit Goyal (CardioNerds Co-Founder) as they interview Dr. Paul Cremer (Associate Director of the Cardiac Intensive Care Unit and Associate Director of the Cardiovascular Fellowship at the Cleveland Clinic) in this broad overview of valvular shock. We discuss the nuances in diagnosis, differing presentations and how physical exam, multi-modality imaging, and invasive hemodynamics can inform management. Audio editing by Dr. Gurleen Kaur (Director of the CardioNerds Internship and CardioNerds Academy Fellow). The CardioNerds Cardiac Critical Care Series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Mark Belkin, Dr. Eunice Dugan, Dr. Karan Desai, and Dr. Yoav Karpenshif. 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 – Cardiogenic Shock and Valvular Heart Disease Shock due to valve disease is the result of a structural abnormality that may be temporized with medical therapy and circulatory support devices. However, it is ultimately best treated with a structural solution in the form of either percutaneous valvular therapies or cardiac surgery. When treating a patient with cardiogenic shock with normal or hyperdynamic ventricular function, we should keep a high index of suspicion for valvular disease. The cardiac output may be reduced due to a stenotic lesion “blocking” forward flow or regurgitant lesion causing backward flow. Acute mitral and aortic regurgitation will typically not manifest as a loud murmur on physical exam. The combination of hypotension and rapid flow of regurgitant blood on an “unprepared” cardiac chamber results in rapid equalization of chamber pressures, shortening the intensity and duration of the murmur. On transthoracic echocardiogram, for instance with acute MR, color Doppler may not show a large turbulent jet, and thus the MR may be underestimated or not appreciated at all. Echocardiography is critical to understand the etiology and severity of valvular shock, and invasive hemodynamics are often needed to guide medical and mechanical interventions. In multi-valve disease with severe aortic stenosis and functional mitral regurgitation, we typically treat the aortic stenosis first, since the mitral regurgitation may improve from the reduction in afterload associated with treating aortic stenosis. Show notes – Cardiogenic Shock and Valvular Heart Disease 1. Shock due to valve disease arises due to a structural problem that may be temporized with medical therapy and circulatory support devices, but is ultimately best treated with a structural solution in the form of either percutaneous valvular therapies or cardiac surgery. Stabilizing therapies for acute mitral regurgitation include afterload reduction with vasodilators, diuresis as needed to reduce pulmonary edema, and mechanical circulatory support including intra-aortic balloon pumps. Therapies for acute aortic regurgitation are typically more limited and include vasopressors such as epinephrine.  Bradycardia should be avoided with agents such as dobutamine or temporary pacing to reduce time in diastole. Temporary mechanical circulatory support options are limited in the setting of acute AR, though case reports of techniques such as LAVA ECMO (left atrial venoarterial extracorpeal membrane oxygenation) as a bridge to definitive therapy have been reported. There are several factors to consider in patients with aortic stenosis and cardiogenic shock. In some patients with aortic stenosis and LV dysfunction, the shock is a result of LV pressure overload potentially leading to congestion, the high afterload introduced on the LV by the stenotic aortic valve, and increased systemic vascular resistance (compensatory for the failing LV). In these patients, acute vasodilators (specifically nitroprusside) can relieve the additive afterload on the LV imposed by increased SVR as a bridge to definitive therapy. In other patients with severe AS, the LV faces high afterload at the level of the aortic valve but the SVR is relatively low (as well as the pressures in the aortic root which can reduce coronary perfusion), and thus these patients may require a pure alpha agonist (e.g., phenylephrine) to reduce the afterload mismatch and reduce myocardial ischemia. Furthermore, when patients have high LV filling pressures, they are reliant on longer diastole times and an atrial kick to promote LV filling and thus rapid atrial fibrillation can be highly detrimental. In both phenotypes, mechanical circulatory support may be needed as a bridge to valve surgery or TAVR. Percutaneous balloon valvuloplasty of the aortic valve may be utilized as a bridge to definitive therapy in select patients In scenarios of valvular disease and cardiogenic shock, right heart catheterization can be helpful to guide and titrate medical therapy and inform decisions to escalate to mechanical circulatory support. Percutaneous therapies (e.g., TAVR or Transcatheter Edge to Edge Repair with MitraClip) are increasingly being utilized as a “primary” therapy on a case by case basis for patients in cardiogenic shock with valvular disease. More data is needed to inform patient phenotypes who would benefit from such a strategy without futility. 2. What is the differential diagnosis for cardiogenic shock with normal or hyperdynamic left ventricular function? One framework to approach cardiogenic shock with normal or hyperdynamic left systolic function is to consider (1) pericardial failure with constriction or tamponade; (2) myocardial failure with severe restrictive disease (3) electrical failure with new arrhythmia, or (4) valvular failure. In this scenario, we should have a high index of suspicion for valvular disease.  The cardiac output may be reduced due to a stenotic lesion blocking forward flow or regurgitant lesion causing backward flow. 3. If I don’t hear a significant murmur on examination, does that rule out an acute regurgitant valvular disease as a cause of shock? Acute mitral and aortic regurgitation may not manifest as a loud murmur on physical exam. In severe, acute AR, a murmur may not be audible if the diastolic pressure in the LV and aorta equilibrate quickly. Similarly, in acute, severe MR, there can be a rapid rise in LA Pressure reducing the driving pressure across the mitral valve. On transthoracic echocardiogram, the same pathophysiology can explain why acute regurgitant lesions may not be readily apparent. For instance, with acute MR, color Doppler may not show a large turbulent jet, and thus the MR may be underestimated or not appreciated at all. In patients with sudden hemodynamic instability after myocardial infarction with hyperdynamic LV function by TTE, for instance, and no other cause for deterioration, TEE can be helpful in evaluating for Acute MR due to papillary muscle or chordal rupture.  4. Echocardiography and guidance with right heart catheterization is helpful to understand the etiology and severity of valvular shock. Echocardiography can help determine whether valve dysfunction is primary (e.g. leaflet perforation due to endocarditis) versus secondary (e.g. dilated left ventricle leading to functional mitral regurgitation), as well as provide clues to the chronicity of valve disease. A right heart catheterization can help inform whether valvular disease is the primary insult or if other factors are contributing, inform an initial management strategy (e.g., medical therapies alone vs. mechanical circulatory support), and assess response to therapy. 5. In multi-valve disease, what is the best way to differentiate which lesion is the culprit? These scenarios are not uncommon and require clinicians to use a multi-modal approach, from patient history, exam, echocardiography, other imaging modalities, and invasive hemodynamics. Identifying the “primary” lesion can still be difficult even after multiple data points. Empiric therapy and assessment of subsequent hemodynamic response may be one way to practically approach multi-valve disease. One scenario covered on the episode was patients with severe aortic stenosis and severe mitral regurgitation. The MR in this scenario may be partly functional due to high LV systolic pressures and may improve with intervention on the aortic valve. Thus, one approach would be to treat AS and evaluate if the MR improves.  References – Cardiogenic Shock and Valvular Heart Disease Erlebach M, Lange R. Multivalvular Disease: Percutaneous Management in 2019 and Beyond. Interv Cardiol. 2019;14(3):142-146. Published 2019 Nov 18. doi:10.15420/icr.2019.13.R1 Khot UN, Novaro GM, Popović ZB, Mills RM, Thomas JD, Tuzcu EM, Hammer D, Nissen SE, Francis GS. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med. 2003 May 1;348(18):1756-63. doi: 10.1056/NEJMoa022021. PMID: 12724481. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2021 Feb 2;143(5):e228] [published correction appears in Circulation. 2021 Mar 9;143(10):e784]. Circulation. 2021;143(5):e35-e71. doi:10.1161/CIR.0000000000000932. Unger P, Clavel MA, Lindman BR, Mathieu P, Pibarot P. Pathophysiology and management of multivalvular disease. Nat Rev Cardiol. 2016;13(7):429-440. doi:10.1038/nrcardio.2016.57. Guest Profiles Dr. Paul Cremer Dr. Paul Cremer earned a Bachelor’s degree in molecular biology from Princeton University, Princeton, NJ, and his medical degree from Harvard Medical School, Boston, MA. Following completion of his internal medicine residency at Massachusetts General Hospital, he worked as a physician for two years at the Navajo IHS Chinle Comprehensive Health Care Facility in Chinle, Ariz. He then continued his postdoctoral training with a three-year fellowship in cardiovascular medicine and a subsequent two-year fellowship in advanced cardiovascular imaging, both at Cleveland Clinic. He joined the Cleveland Clinic staff in 2017. He is the director of the Cleveland Clinic CCU.  He enjoys swimming and reading fantasy books with his daughters. He joins the cardionerds cardiology podcast to shed insight on cardiac amyloid imaging. Dr. Pranoti Hiremath Dr. Pranoti Hiremath is an interventional cardiology fellow at Johns Hopkins. She completed her MD at HMS, did her residency in Internal Medicine at University of Washington, and her Cardiology fellowship of Hopkins. CardioNerds Cardiac Critical Care Production Team Karan Desai, MD Dr. Mark Belkin Dr. Yoav Karpenshif Amit Goyal, MD Daniel Ambinder, MD

The following question refers to Section 4.8 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Christian Faaborg-Andersen, answered first by UCSF resident Dr. Jessie Holtzman, and then by expert faculty Dr. Melissa Tracy. Dr. Tracy is a preventive cardiologist, echocardiographer, Director of Cardiac Rehabilitation, and solid organ transplant cardiologist at Rush University. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #6 A 62-year-old man with a history of non-obstructive coronary artery disease, heart failure with reduced ejection fraction (EF 30-35%), stage III chronic kidney disease, and type II diabetes mellitus presents to your clinic to establish care. His only medications are aspirin 81 mg daily and metformin 1000 mg BID, which he has taken since being diagnosed with diabetes mellitus 5 years ago. His hemoglobin A1c is 6.8%. What changes would you recommend to his medications at this time? A. Start glipizideB. Start saxagliptinC. Start empagliflozinD. No changes Answer #6 The correct answer is C – start empagliflozin. The Trials involving SGLT-2 inhibitors and GLP-1R agonists have shown cardiovascular benefits independent of glycemic control and metformin use. The ADA recommends metformin as a first-line therapy for all patients with type 2 DM. The ESC also recommends metformin as first-line therapy but only in patients without ASCVD, CKD, or HF (Class I, LOE B). If a patient has ASCVD, metformin can be considered (Class IIa, LOE B). Rather, for those patients with type 2 DM and ASCVD, the ESC recommends the use of GLP-1R agonist or SGLT-2 inhibitors with proven outcome benefits to reduce CV and/or cardiorenal outcomes (Class I, LOE A). Additionally, for those with type 2 DM and either CKD or HFrEF, the ESC recommends the use of SGLT-2 inhibitor to improve outcomes (Class I, LOE A). In contrast to the ADA, the view of the ESC is that metformin should be considered but is not mandatory first-line treatment in patients with diabetes and ASCVD or evidence of target organ damage. The initiation of metformin in such patients should not forego or delay the initiation of evidence-based SGLT2 inhibitors or GLP-1RAs. Therefore, the next best step for our patient is to start an SGLT-2 inhibitor given his history of CAD, HF, and CKD. While this patient’s A1c goal is within the range recommended for patients with Type 2 DM and ASCVD (<7%), given his CAD, HF, and CKD an SGLT-2 inhibitor should still be added. Saxagliptin is a DPP-4 inhibitor, a class of drugs that showed no effect of MACE but increased risk of HF hospitalization in patients with DM and existing. Lifestyle management is a top priority for ASCVD prevention and management of DM. Lifestyle intervention lowers future microvascular and macrovascular risks as well as mortality in the longer term. Intensive lifestyle changes with low-calorie diets and mean weight losses in the region of 10 kg leads to remission of type 2 DM in around 46% of cases at 1 year and 36% by 2 years. Smoking cessation, a diet low in saturated fat and high in fiber, aerobic physical activity, strength training, and reduction in energy intake for weight optimization are all recommended for patient with diabetes mellitus (Class I). Main Takeaway In patients with Type 2 DM and ASCVD or end organ dysfunction, SGLT-2 inhibitors or GLP-1R agonists should be recommended regardless of background therapy or glycemic control. For patients with type 2 diabetes mellitus and CKD or HFrEF, SGLT-2 inhibitor is recommended. Guideline Location Section 4.8.1, Pages 3289-90. CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 4.10 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern student Dr. Christian Faaborg-Andersen, answered first by UCSD fellow Dr. Patrick Azcarate, and then by expert faculty Dr. Laurence Sperling. Dr. Laurence Sperling is the Katz Professor in Preventive Cardiology at the Emory University School of Medicine and Founder of Preventive Cardiology at the Emory Clinic. Dr. Sperling was a member of the writing group for the 2018 Cholesterol Guidelines, serves as Co-Chair for the ACC’s Cardiometabolic and Diabetes working group, and is Co-Chair of the WHF Roadmap for Cardiovascular Prevention in Diabetes. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #5 The European Society of Cardiology Prevention guidelines currently recommend that low-dose colchicine (0.5mg/day) may be considered for the primary prevention of cardiovascular disease. A. TrueB. False Answer #5 The correct answer is False.  The correct answer is False. The European Society of Cardiology recommends that low-dose colchicine may be considered as an adjunctive therapy for secondary rather than primary prevention of cardiovascular disease in individuals whose risk factors are otherwise insufficiently controlled (Class IIb, LOE A). A broad evidence base currently supports that inflammation has pro-atherosclerotic effects and that reducing inflammation may reduce atherogenesis in high-risk patients. The initial LoDoCo trial in 2013 first demonstrated a 10.7% absolute risk reduction in acute coronary syndrome, out of hospital cardiac arrest, and non-cardioembolic ischemic stroke with daily low-dose colchicine; however, results were clouded by small sample size. Subsequently, the CANTOS trial in 2017 demonstrated a 15% relative reduction in non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death with Canakinumab, an anti-inflammatory monoclonal antibody inhibitor of interleukin-1. More recently, the COLCOT trial in 2019 studying patients with recent AMI and LoDoCo2 trial in 2021 studying patients with stable chronic CAD both demonstrated reductions in myocardial infarction, cardiovascular mortality, CVA, and ischemia-driven revascularization with colchicine 0.5mg/day. In the LoDoCo2 trial, stable CAD was defined either angiographically, by coronary CT, CAC >400, or history of CABG >10 years prior with evidence of failed grafts or angioplasty since that time. In high-risk individuals with stable ischemic heart disease, the most recent evidence suggests that once daily low dose colchicine may reduce myocardial infarction and other ischemic events. Future studies may assess the biochemical markers including the trend of lipids and inflammatory markers to identify subpopulations that may benefit most from this therapy. Main Takeaway: Based upon the 2021 ESC Prevention Guidelines, clinicians may consider initiating low-dose colchicine (0.5mg/day) for secondary prevention of cardiovascular disease, particularly if other risk factors are insufficiently controlled or if recurrent CVD events occur despite optimal therapy. Guideline Location:  Section 4.10, page 3291. CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

Dr. Roger Blumenthal, Director of the Ciccarone Center for the Prevention of Cardiovascular Disease at Johns Hopkins, discusses guidelines for cardiovascular prevention. They cover the management of hypertension in a 40-year-old woman, emphasizing lifestyle interventions and combination therapy. They also discuss the assessment of risk and antiplatelet therapy for blood pressure management, highlighting the importance of lifestyle changes and a two-drug combination approach.