Cardionerds: A Cardiology Podcast

CardioNerds (Amit and Dan) join join Dr. Andrew Dicks (Vascular medicine physician at Prisma Health, former fellow at Mass General Vascular) and Dr. Prateek Sharma (Vascular interventional & medicine fellow at MGH) for an ice-cold drinks at the Esplanade in Boston, MA to discuss a case about a patient who developed a pulmonary embolism and masterfully discuss the diagnosis and management of of pulmonary emboli. Dr. Ido Weinberg (Director, Vascular Medicine Fellowship at MGH) provides the ECPR for this episode. Case Abstract: A 59-year-old Spanish-speaking man with no significant past medical history presents after falling 15-20 feet from a ladder and landing on his back. He was found to have an L1 fracture and left radial fracture and underwent T12-L2 fusion with neurosurgery on hospital day 1 and ORIF of left radial fracture with orthopedic surgery on hospital day 2. On hospital day 5, he develops acute onset tachycardia with HR in the 130s bpm with new O2 requirement associated with mild shortness of breath at rest without any chest discomfort. His labs were notable for an elevated troponin and proBNP. He underwent CTPA which demonstrated acute bilateral occlusive pulmonary emboli (PE) extending in the right and left main pulmonary arteries. TTE demonstrated right ventricle dilation. The patient was started on a heparin infusion and a PE response team (PERT) meeting was held to discuss treatment options. Given recent surgery, use of thrombolytic therapy was felt to be too risky and thus he was taken for percutaneous thrombectomy in the cath lab. PA pressure prior to intervention was 51/21 mmHg. The patient underwent suction thromboembelectomy with the Flow Triever device with extraction of thrombus and improvement in PA pressure to 19/11 mmHg. He was treated with anticoagulation thereafter and discharged home two days after the procedure. 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 Acute bilateral occlusive and nonocclusive pulmonary emboli extending from the right and left main pulmonary arteries to the lobar and segmental arteries of all the lobes.  Moderate right heart strain including the right atrium and the right ventricle. RV/LV ratio > 1.0. Right ventricular cavity is dilated (RV size at the base measures to 45mm). Right ventricular systolic function is moderately decreased. Right ventricular free wall is hypokinetic with sparing of the right ventricular apex consistent with acute right ventricular strain Pulmonary angiography demonstrated extensive proximal bilateral PEs Caption: Post-procedure TTE demonstrated resolution of RV strain with normalization of RV size and function. Episode Schematics & Teaching Pearls While there are markers to suggest PE, such as ECG findings or evidence of RV dilatation, a PE cannot be confirmed without imaging. Elevation of cardiac biomarkers and evidence of RV dysfunction are used to risk stratify PE, not the degree of thrombus burden or locale of thrombus. Enoxaparin is the preferred anticoagulant to initiate at time of PE diagnosis if comorbidities allow. Optimal treatment of intermediate risk PE remains uncertain as there is little data about long-term outcomes. Aggressive treatment should be used judiciously and chosen on a case-by-case basis. PE response teams (PERT) allow for multidisciplinary expert opinion in the face of scarce evidence to determine what is felt to be the best management strategy. Notes 1. What is a PERT team and why is it helpful? We have several tools and approaches for the management of PE. There are also many subspecialities involved in the care of patients with PE, including vascular medicine, intervention cardiology, hematology, pulmonology, cardiac surgery, radiology, emergency department, intensive care, and more. As such, the best treatment plan for a given patient with PE can be challenging, especially if the services involved in treatment of the PE function in silos. PERT, or PE Response Team, was built to address this concern. It is a multidisciplinary team that originated at MGH whose goal is to coordinate care for high-risk PE patients and advance PE-related care in the institution. PERT allows for multidisciplinary expert opinion in the face of scarce evidence to determine what is felt to be the best management strategy. 2. How do we risk stratify patients with PE? Risk stratification is largely dependent on the hemodynamic significance caused by the PE. In addition to vital sign derangement, patients with PE should also be evaluated for evidence of cardiac strain due to PE by checking for evidence of RV dilatation on CT or TTE and for elevation of cardiac biomarkers. The combination of this information is used to risk stratify patients. Additionally, risk stratification tools, such as the PESI and sPESI scores, are used to guide risk stratification. Based on the ESC 2019 guidelines, PEs are stratified into high risk, intermediate-high risk, intermediate-low risk, or low risk. High risk: evidence of hemodynamic instability as defined by hypotension or shock. Intermediate-high risk: evidence of both RV dysfunction on imaging AND elevated cardiac biomarkers in the absence of HD instability Intermediate-low risk: evidence of either RV dysfunction on imaging OR elevated cardiac biomarkers in the absence of HD instability Low risk: no evidence of cardiac dysfunction on imaging or labs and no evidence of HD instability. Risk stratification is important as it helps guide medical management of patients. Important factors that have not been associated with PE severity include degree of thrombus burden and location of clot. 3. What do we know about optimal management of patients with intermediate risk PE? Unfortunately, data is fairly limited with regards to the optimal management strategy for patients with intermediate risk PE, namely whether anticoagulation alone is sufficient versus if a patient would benefit from more advanced therapies. All patients should be started on anticoagulation, preferably SQ enoxaparin if comorbidities allow, as soon as possible (if there are no contraindications to anticoagulation). However, choosing which patients would benefit from more advanced therapies remains limited. Thrombolysis has been associated with lower all-cause mortality in patients with intermediate-risk PE when compared to anticoagulation alone. However, not surprisingly, thrombolysis was also associated with more major bleeding, including intracranial hemorrhage. In the ULTIMA trial, catheter directed thrombolysis was shown to improve RV dysfunction more quickly compared to anticoagulation at 24 hours. However, at 90 days, there was no difference in degree of RV dysfunction between the two groups. Percutaneous thrombectomy devices have been shown to be safe and effective at reducing RV size. However, there are no head-to-head comparisons of these modalities versus anticoagulation or thrombolysis and data is limited regarding the long-term efficacy. Choosing the correct patient to proceed with advanced therapies remains challenging and the decision is often made on a case-by-case basis. There are ongoing randomized control trials that will hopefully assist in guiding this decision making. 4. What about management for those with high-risk PE? High risk PEs mandate aggressive and rapid treatment. Thrombolysis has been shown to have a mortality benefit compared to anticoagulation.  Catheter directed thrombolysis can be considered in high-risk PE; however, rapid implementation needs to be available. VA-ECMO has also been demonstrated to reduce mortality in these patients. 5. What additional treatment options are available for patients with PE who are not improving on anticoagulation and have a contraindication to thrombolytic therapy? There are several contraindications to thrombolytic therapy, including recent surgery, CVA, or bleeding. Percutaneous and surgical thrombectomy should be considered in these patients. Surgical thrombectomy is effective but does require significant anticoagulation during the surgery while the patient is on cardiac bypass. For this reason, patients that have a contraindication to thrombolysis might not be able to tolerate the high levels of anticoagulation required for the surgery and thus a surgical thrombectomy might not be a feasible option. There are several percutaneous thrombectomy devices on the market currently which have been shown to be safe and effective at reducing the RV size in the acute period. Because these devices do not require thrombolytic agents, the risk of bleeding is lower and there is less ICU utilization. However, there have not been head-to-head comparisons between these devices and other treatment modalities. References Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405 Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2017;2:CD001100. doi:10.1002/14651858.CD001100.pub4 Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411. doi:10.1056/NEJMoa1302097 Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421. doi:10.1001/jama.2014.5990 Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479-486. doi:10.1161/CIRCULATIONAHA.113.005544 Subramaniam RM, Mandrekar J, Chang C, et al. Pulmonary embolism outcome: a prospective evaluation of CT pulmonary angiographic clot burden score and ECG score. AJR Am J Roentgenol. 2008;190(6):1599-1604. doi:10.2214/AJR.07.2858 Jain CC, Chang Y, Kabrhel C, et al. Impact of Pulmonary Arterial Clot Location on Pulmonary Embolism Treatment and Outcomes (90 Days). Am J Cardiol. 2017;119(5):802-807. doi:10.1016/j.amjcard.2016.11.018 Tu T, Toma C, Tapson VF, et al. A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study. JACC Cardiovasc Interv. 2019;12(9):859-869. doi:10.1016/j.jcin.2018.12.022

CardioNerds (Daniel Ambinder) and ACHD series co-chair Dr. Dan Clark discuss advanced heart failure therapies including mechanical circulatory support (MCS) and heart transplantation (HT) in patients with adult congenital heart disease (ACHD) with Dr. Rafael Alonso-Gonzalez, cardiologist and director of Adult Congenital Heart Disease program at the University of Toronto and ACHD fellow Dr. Andy Pistner (University of Washington). They cover epidemiology of heart failure in ACHD, outcomes after HT, unique challenges of HT in this population, impact of allocation policies on access to transplantation, and regionalization of advanced heart failure care. They also discuss a practical approach to advanced heart failure therapy evaluation in ACHD. Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares. 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 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. 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 – Advanced Heart Failure Therapies (MCS/HT) Among ACHD Patients Heart failure is a major comorbidity and the leading cause of death in adults with congenital heart disease. Identification of advanced heart failure in ACHD is challenging. ACHD patients do not always self-identify exercise limitations or exertional dyspnea. Cardiopulmonary exercise testing is a useful tool in evaluating these patients. Patients with ACHD awaiting heart transplantation are less likely than non-ACHD patients to receive a heart transplant, and ACHD patients have an increased risk of death or delisting while awaiting heart transplantation. Evaluation of transplant candidacy and potential need for multi-organ transplantation in complex congenital heart disease (i.e., Fontan palliation) requires a multidisciplinary approach. Regionalization of care improves outcomes for ACHD patients with advanced heart failure. High volume transplant centers have better early survival for ACHD patients after heart transplant, and the highest volume ACHD transplant centers in each UNOS region have better early survival. Show notes – Advanced Heart Failure Therapies (MCS/HT) Among ACHD Patients 1. How many ACHD patients have heart failure? Patients with ACHD are a large and heterogeneous group. The signs and symptoms of heart failure vary widely depending on the underlying congenital heart disease. Patients with D-transposition of the great arteries repaired with an arterial switch operation have low rates of heart failure (~3%)1 compared to those patients Fontan palliation for single ventricle physiology (40%)2. Heart failure is the leading cause of death in patients with ACHD3,4. 2. How many patients with ACHD end up receiving a heart transplant or mechanical circulatory support? Heart transplantation for congenital heart disease in adults has been increasing in frequency since the late 1980s. Between 2010 and 2012, this accounted for 4% of all adult heart transplants in the United States5. This represents a small fraction compared to the number of adults who die due to complications of heart failure related to congenital heart disease. In a recent study of the INTERMACs registry, 126 patients with ACHD from a total of 16,000 patients over a 10-year period underwent placement of durable mechanical support devices (ventricular assist device)6. 3. Why are these numbers low relative to the number of ACHD patients with heart failure? Identification of those patients with ACHD who are at risk for adverse outcomes related to heart failure is challenging. The symptoms of heart failure reported in these patients is often different from what is described in patients with acquired heart failure. Similarly, having grown up with reduced aerobic capacity, many of these patients do not self-identify exercise limitations or exertional dyspnea7. The organ allocation policies that are used to prioritize patients for transplant also contribute to this situation. Patients with ACHD on the heart transplant wait-list are less likely than their non-ACHD counterparts to receive a transplant. This difference persists regardless of initial urgency listing status8. Secondly, patients with ACHD are more likely to die or be delisted (presumably due to clinical deterioration) while awaiting heart transplantation9. The US heart allocation policies have recently been updated, which may improve access to heart transplantation in this population. Other barriers to heart transplantation in patients with ACHD include allosensitization (development of antibodies against potential donor antigens), donor-recipient size matching, psychosocial barriers, and anatomic or other surgical challenges. Lastly, there are few providers with training in both advanced heart failure and adult congenital heart disease to integrate the evaluations necessary to identify suitable candidates for transplantation. 4. How do patients with ACHD do after heart transplantation? Patients with ACHD have a worse early mortality after heart transplant (up to 1 year) compared to those patients without ACHD10. However, early survival after heart transplantation in ACHD has been improving over the past 20 years11. Additionally, those patients with ACHD who survive past the first year after heart transplantation have improved survival compared to patients without congenital heart disease. More recently, we have found that that patients with ACHD undergoing heart transplant at high-volume centers (>38 transplants per year) have improved early survival compared to low-volume centers (<14 transplants per year)12. Overall survival is also improved when heart transplantation is performed at the highest volume ACHD transplant center in the UNOS region when compared to all the other transplant centers13. This idea of regionalization of care holds promise for transplant outcomes in this population. References – Advanced Heart Failure Therapies (MCS/HT) Among ACHD Patients Khairy P, Clair M, Fernandes SM, et al. Cardiovascular outcomes after the arterial switch operation for D-transposition of the great arteries. Circulation. Jan 22 2013;127(3):331-9. doi:10.1161/CIRCULATIONAHA.112.135046 Piran S, Veldtman G, Siu S, Webb GD, Liu PP. Heart failure and ventricular dysfunction in patients with single or systemic right ventricles. Circulation. Mar 12 2002;105(10):1189-94. doi:10.1161/hc1002.105182 Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Mortality in adult congenital heart disease. Eur Heart J. May 2010;31(10):1220-9. doi:10.1093/eurheartj/ehq032 Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of death in adults with congenital heart disease. The American Journal of Cardiology. 2000;86(10):1111-1116. doi:10.1016/s0002-9149(00)01169-3 Maxwell BG, Wong JK, Sheikh AY, Lee PH, Lobato RL. Heart transplantation with or without prior mechanical circulatory support in adults with congenital heart disease. Eur J Cardiothorac Surg. May 2014;45(5):842-6. doi:10.1093/ejcts/ezt498 Cedars A, Vanderpluym C, Koehl D, Cantor R, Kutty S, Kirklin JK. An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of hospitalization, functional status, and mortality after mechanical circulatory support in adults with congenital heart disease. J Heart Lung Transplant. May 2018;37(5):619-630. doi:10.1016/j.healun.2017.11.010 Gratz A, Hess J, Hager A. Self-estimated physical functioning poorly predicts actual exercise capacity in adolescents and adults with congenital heart disease. Eur Heart J. Feb 2009;30(4):497-504. doi:10.1093/eurheartj/ehn531 Everitt MD, Donaldson AE, Stehlik J, et al. Would access to device therapies improve transplant outcomes for adults with congenital heart disease? Analysis of the United Network for Organ Sharing (UNOS). J Heart Lung Transplant. Apr 2011;30(4):395-401. doi:10.1016/j.healun.2010.09.008 Alshawabkeh LI, Hu N, Carter KD, et al. Wait-List Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation in the U.S. J Am Coll Cardiol. Aug 30 2016;68(9):908-17. doi:10.1016/j.jacc.2016.05.082 Menachem JN, Schlendorf KH, Mazurek JA, et al. Advanced Heart Failure in Adults With Congenital Heart Disease. JACC Heart Fail. Feb 2020;8(2):87-99. doi:10.1016/j.jchf.2019.08.012 Riggs KW, Zafar F, Radzi Y, Yu PJ, Bryant R, 3rd, Morales DLS. Adult Congenital Heart Disease: Current Early Expectations After Cardiac Transplantation. Ann Thorac Surg. Feb 2020;109(2):480-486. doi:10.1016/j.athoracsur.2019.06.067 Menachem JN, Lindenfeld J, Schlendorf K, et al. Center volume and post-transplant survival among adults with congenital heart disease. J Heart Lung Transplant. Nov 2018;37(11):1351-1360. doi:10.1016/j.healun.2018.07.007 Nguyen VP, Dolgner SJ, Dardas TF, Verrier ED, McMullan DM, Krieger EV. Improved Outcomes of Heart Transplantation in Adults With Congenital Heart Disease Receiving Regionalized Care. J Am Coll Cardiol. Dec 10 2019;74(23):2908-2918. doi:10.1016/j.jacc.2019.09.062 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/ CardioNerds Adult Congenital Heart Disease Production Team Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal), Dr. Colin Blumenthal (CardioNerds Academy House Faculty Leader and FIT at the University of Pennsylvania), and Dr. Anjali Wagle (CardioNerds Ambassador and FIT at Johns Hopkins University), discuss the baseline assessment of stroke and bleeding risk in patients with atrial fibrillation (AF) with Dr. Elaine Hylek. Dr. Hylek is a professor of medicine at the Boston University School of Medicine and is the Director of the Thrombosis and Anticoagulation Service at Boston Medical Center. Stroke is a potentially devastating and preventable complication of AF. Understanding the balance between stroke and bleeding risk is crucial in determining who should be on anticoagulation. Join us to discuss this topic! In the next episode of the series, we will discuss situational risk assessment in the context of peri-cardioversion, peri-procedural status, triggered atrial fibrillation, and more. Audio editing by CardioNerds Academy Intern, Pace Wetstein. This CardioNerds Atrial Fibrillation 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. Kelly Arps and Dr. Colin Blumenthal. This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. We have collaborated with VCU Health to provide CME. Claim free CME here! Disclosures: Dr. Hylek discloses grant and research support from Medtronic and Janssen, and honoraria and/or consulting fees from Boehringer Ingelheim, and Bayer. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Atrial Fibrillation 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 – Atrial Fibrillation: Assessment of Stroke & Bleeding Risk The CHA2DS2-VASc should be used to determine stroke risk in all patients. It was updated from the CHADS2 score to better separate patients into high and low risk and a score of 0 has a very low risk of a stroke. Understanding a given model’s derivation is key to application for any risk model. Understanding who was and was not included when a risk score was derived helps determine how to clinically use it. For example, mechanical valves, hypertrophic cardiomyopathy, cardiac amyloidosis, and moderate to severe MS were all excluded or poorly represented and should receive AC in AF regardless of CV. The HAS-BLED score should be used to identify modifiable risk factors for bleeding and address them. It is less useful to determine when we should stop AC. Factors that go into the score are dynamic and the intention was to alert the provider of potentially modifiable factors that could be addressed to lower bleeding risk (such as better BP control). Fear the clot. Patients should be on AC unless there is a serious contraindication as embolic strokes can be devastating with a high mortality (~24% mortality at 30 days) “What am I saying by not writing the prescription… I am saying that it’s OK to have an ischemic stroke.” Survey data shows that patients are willing to experience 3.5 GI bleeds on average before 1 stroke, so favoring AC is often a patient centered approach Notes – Atrial Fibrillation: Assessment of Stroke & Bleeding Risk Notes drafted by Dr. Anjali Wagle 1. Why do strokes happen in atrial fibrillation? Why is reducing stroke risk so important? Atrial fibrillation is associated with a significantly increased risk of stroke. The mortality of strokes related to AF have been estimated to be around 25% at 30 days in early studies which included either persistent or permanent AF, though of note, these studied were biased towards larger strokes since the diagnosis was based on physical exam and not high resolution imaging. AF promotes thrombogenesis through Virchow’s triad which includes: Abnormal blood flow Endothelial damage Hypercoagulability In atrial fibrillation, patients usually have a dilated left atrium and decreased blood flow through the atrial appendage which contribute to thrombogenesis. Multiple risk scores have been derived (i.e., CHA2DS2VASc) for estimation of stroke risk in patient with AF to identify whom to treat with anticoagulation to reduce the stroke risk. 2. How were CHADS2 and CHA2DS2VASc (CV) created and validated? The CHADS2 score was derived in 2001 by Gage et al from data including hospitalized patients with nonrheumatic AF who were not prescribed warfarin at hospitalized discharge. The CHADS2 score assigns one point to congestive heart failure, hypertension, age ≥ 75 years, and diabetes mellitus and two points to a previous history of stroke or transient ischemic attack (TIA) for a total of 6 points. Stroke rate per 100 patient-years rose by a factor of 1.5 for each 1-point increase in the CHADS2 score. However, it was found that there were several limitations associated with the CHADS2 score including that more than half of the patients were classified as moderate risk, making it unclear if antiplatelet or anticoagulation should be used in this population. Additionally, there were other “minor” risk factors (female sex, CAD, age 65-74) that were not included in the score. In 2010, Lip et al proposed the CHA2DS2VASc score that included these three additional factors: female gender, vascular events, and age 65-74. These additions to the original CHADS2 score allowed the CHA2DS2VASc score to reclassify patients in the moderate risk group into either the high or low risk groups (CV <1 or >2), making the decision of when to start anticoagulation easier. Some weaknesses of the CV score include that the individual factors are binary. For example, one point for diabetes does not discriminate risk based on if the patient’s A1c is 14 vs. 7. Similarly, the score is static and assumes the risk from each risk factor doesn’t change over time even though the endothelial dysfunction caused by a specific disease state isn’t fixed. Additionally, the C-statistic for the CV score is only 0.6 with newer scores that are more accurate including such as GARFIELD-AF (but these newer scores are less user friendly). That being said, the score still does a very good job of differentiating between high and low risk patients, which is the most important clinical question when deciding if someone needs anticoagulation. 3. Which populations were not studied in the validation of the CV score? Many of these studies have woefully low enrollment of racially diverse populations. Additionally, patients with amyloidosis, moderate-severe MS, and HOCM have a baseline higher risk of stroke were excluded from these studies. Patients with bioprosthetic valves were also excluded from the original derivation though there is now limited data showing use of the CV is reasonable. 4. How does AF burden affect stroke risk? Is there a temporal association between AF and stroke? Early trials did not find a temporal association between AF and stroke, though these trials often used physical exam definitions for stroke and current technology like implantable loop recorders (ILRs) didn’t exist to monitor 24/7. More modern studies like the TREND and KP-RHYTHM trials showed that stroke risk is related to AF burden. Longer episodes of AF seem to clearly be associated with stroke, but shorter episodes of AF aren’t as temporally related to stroke. In the LOOP trial use of ILRs to detect episodes of AF longer than 6 minutes led to a 3-fold increase in AF detection and initiation of AF, but did not reduce the number of strokes. This could indicate that there is some amount of AF that doesn’t require AC or that short runs of AF are associated with atrial myopathy that could be causing the strokes. It remains unclear what is the “chicken and egg” in this scenario. 5. How can we assess bleeding risk for patients with atrial fibrillation? How can we use these scores in our clinical practice? Developed and published in 2010 by Pisters et al., the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly [age >65], medication predisposing to bleeding, excessive alcohol use) score aimed to create an easy to calculate and clinically meaningful score to estimate bleeding risk. It was validated using 3,978 patients from the Euro Heart Survey on AF and had good predictive accuracy (C-statistic 0.72). Of note, the score uses the less severe ISTH definition for a major hemorrhage, which doesn’t require as severe bleeding as the TIMI major bleeding definition. Many of the factors that go into the score are dynamic (for example HTN is SBP > 160 and not a history of HTN). The intention was to alert the provider of potentially modifiable factors that could be addressed to lower bleeding risk (such as better BP control). This would reduce the patients HAS-BLED score and therefore their bleeding risk. There is no absolute cutoff where anticoagulation in AF would be considered prohibitive. 6. What is the approach for patients with borderline stroke risk with a CV of 1 in men or 2 in women? Patients with a CV of 1 have between a 0.6% and a 0.9% risk of stroke/TIA/systemic embolism in a given year. That means even with a CV of 1 they have close to a 1/100 risk of an event in a given year. Given the high mortality and morbidity with embolic strokes and the lower incidence of major bleeding with modern DOACs, should have shared decision-making conversation with patients about starting AC at this risk level. One can consider other risk factors not in CV like LA function, appendage morphology, AF burden etc to help as tie breakers. References – Atrial Fibrillation: Assessment of Stroke & Bleeding Risk Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010 Nov;138(5):1093-100. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864–2870. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society. Journal of the American College of Cardiology. 2006;48(4):e149-e246. doi:10.1016/j.jacc.2006.07.018 Lip GY, Lim HS. Atrial fibrillation and stroke prevention. The Lancet Neurology. 2007;6(11):981-993. doi:10.1016/S1474-4422(07)70264-84. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation. Ann Intern Med. 2007;146(12):857-867. doi:10.7326/0003-4819-146-12-200706190-00007 van Doorn S, Debray TPA, Kaasenbrood F, et al. Predictive performance of the CHA2DS2-VASc rule in atrial fibrillation: a systematic review and meta-analysis. Journal of Thrombosis and Haemostasis. 2017;15(6):1065-1077. doi:10.1111/jth.13690 Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach. Chest. 2010;137(2):263-272. doi:10.1378/chest.09-1584 Okumura K, Inoue H, Atarashi H, et al. Validation of CHA2DS2-VASc and HAS-BLED Scores in Japanese Patients With Nonvalvular Atrial Fibrillation: – An Analysis of the J-RHYTHM Registry –. Circ J. 2014;78(7):1593-1599. doi:10.1253/circj.CJ-14-0144

With the advent and rapid evolution of contemporary percutaneous coronary intervention (PCI), the early invasive management of acute myocardial infarction (AMI) has become a mainstay in therapy with significant impact on patient outcomes. However, despite modern advances in technology and system-based practices, AMI presenting with cardiogenic shock (CS) continues to portend a high risk of morbidity and mortality. Few randomized controlled clinical trials are available to guide decision-making in this uniquely challenging patient population. Understanding the pathophysiologic mechanism by which injury occurs and propagates the shock cycle can be instrumental in selecting an appropriate strategy for revascularization and left ventricular unloading. In this episode we are joined by Dr. Venu Menon, The Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine,  section head of clinical cardiology, fellowship program director, and director of the Cardiac intensive care unit at the Cleveland Clinic. Dr. Menon shares his wealth of knowledge and experience to help us review the contemporary data available for AMI CS management in a case-based discussion. We are also joined by Dr. Priya Kothapalli, star chief fellow and future interventionalist from University of Texas at Austin, series co-chair Dr. Yoav Karpenshif, and CardioNerds Co-founders Amit Goyal and Daniel Ambinder. Audio editing by CardioNerds Academy Intern, Dr. Christian Faaborg-Andersen. 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. 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. 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 – Approach to Acute Myocardial Infarction Cardiogenic Shock with Dr. Venu Menon The H&P does matter! Age, location of infarction, heart rate, systolic blood pressure, and heart failure symptoms all carry weight in determining prognosis and risk of mortality. Define functional status, comorbid conditions, and life expectancy to help guide clinical decision-making. Do a quick bedside echocardiogram if possible to elucidate the predominant mechanism driving CS and rule out mechanical complications. Act with urgency! Get to the catheterization lab to characterize coronary anatomy and revascularize the culprit vessel as soon as possible. Minimize/avoid the use of vasopressors; if needed, wean as quickly as possible to avoid worsening myocardial ischemia. Consider mechanical circulatory support early! Despite dramatic advances in AMI management, data is limited in AMI CS management. Ask the important questions, get involved in the scientific inquiry as a trainee! Show notes – Approach to Acute Myocardial Infarction Cardiogenic Shock with Dr. Venu Menon 1. Why is it important to recognize AMI complicated by CS? AMI CS occurs in 7-10% of patients presenting with AMI and has a higher prevalence among elderly patients. The SHOCK trial (1999) showed significant survival benefit at 6 months with early revascularization with balloon angioplasty compared to medical therapy alone in AMI CS. Registry data suggests that early revascularization is beneficial in AMI CS even in elderly patients. Decision-making should be guided using a holistic view of the patient’s overall biology. Despite advances in revascularization techniques and availability of mechanical support, AMI CS portends a 40-45% risk of 30-day mortality in the modern era. Significant variation in management strategy exists between centers and data to guide decision-making is limited. The Society for Cardiovascular Angiography and Intervention (SCAI) classification system of shock stage may be helpful in characterizing patient risk and guiding clinical decision-making. 2.     Which patients with AMI CS should undergo invasive monitoring and revascularization? What should be the timing of any intervention? In viable patients presenting with AMI CS, the primary goal should be to get to the catheterization laboratory to characterize the anatomy and revascularize the culprit vessel as soon as possible. Patient history, physical exam, laboratory exam, and echocardiography, if available, are critical pieces of information that should be obtained without delaying catheterization laboratory transfer. Patients presenting in SCAI shock stages C-E may require stabilization pre-procedure while minimizing delays to revascularization. Anticipating potential sequelae (such as acute pulmonary edema with respiratory failure requiring intubation) is crucial to minimizing delays. Maintain adequate perfusion pre-procedure (goal mean arterial blood pressure of >65mmHg). Minimize use and avoid escalation of vasopressor or inotropic therapy, as these agents worsen myocardial ischemia. The prevalence of multivessel disease, left main or proximal left anterior descending artery disease in AMI CS is high. Revascularization with restoration of TIMI 3 flow as soon as possible should be the primary goal, regardless of strategy. 3.     When should mechanical circulatory support (MCS) be used in AMI CS? Immediate MCS may be beneficial in patients with persistent hemodynamic or electrical instability or patients at high risk for developing instability. MCS should be placed early and maintained until the shock cycle is reversed. If the primary mechanism for CS is left ventricular failure, an intra-aortic balloon pump (IABP) or transvalvular axial flow pump (Impella) may be considered. Additional strategies include venoarterial extracorporeal membrane oxygenation with left ventricular venting strategy or TandemHeart percutaneous assist device. There is limited data regarding the role of MCS in AMI; this is an area of active clinical investigation. Mechanistically, MCS provides the obvious benefits of supporting systemic perfusion while reducing cardiac workload; risks include bleeding, thrombosis, hemolysis, limb ischemia, and other vascular complications. MCS should be weaned slowly using multiple clinical and hemodynamic parameters, including Swan Ganz catheter data. If unable to wean MCS due to insufficient myocardial recovery despite support over a prolonged period in the setting of adequate revascularization, additional options such as durable MCS, heart transplantation, or palliative care should be considered. 4.     What is the current evidence base for culprit-only vs. complete revascularization in AMI CS? The CULPRIT-SHOCK trial showed an increased 30-day and 1-year risk of a composite of all-cause mortality and need for renal replacement therapy in patients that underwent culprit and immediate non-culprit vessel revascularization in AMI CS. While there is no definitive data to support complete revascularization in AMI CS, this strategy may be considered in patients with multiple possible culprit lesions or subtotal non-culprit lesions with reduced TIMI grade flow corresponding with wall motion abnormality and normal wall thickness suggestive of viable myocardium. References – Approach to Acute Myocardial Infarction Cardiogenic Shock with Dr. Venu Menon Tehrani BN, Truesdell AG, Psotka MA, et al. A Standardized and Comprehensive Approach to the Management of Cardiogenic Shock. JACC Hear Fail. 2020;8(11):879-891. doi:10.1016/j.jchf.2020.09.005 Kapur NK, Davila CD. Timing, timing, timing: the emerging concept of the ‘door to support’ time for cardiogenic shock. Eur Heart J. 2017;38(47):3532-3534. doi:10.1093/eurheartj/ehx406 Hochman JS, Sleeper LA, Webb JG, et al. Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock. N Engl J Med. 1999;341(9):625-634. doi:10.1056/NEJM199908263410901 Ibanez B, Halvorsen S, Roffi M, et al. Integrating the results of the CULPRIT-SHOCK trial in the 2017 ESC ST-elevation myocardial infarction guidelines: viewpoint of the task force. Eur Heart J. 2018;39(48):4239-4242. doi:10.1093/eurheartj/ehy294 Shah AH, Puri R, Kalra A. Management of cardiogenic shock complicating acute myocardial infarction: A review. Clin Cardiol. 2019;42(4):484-493. doi:10.1002/clc.23168 Basir MB, Kapur NK, Patel K, et al. Improved Outcomes Associated with the use of Shock Protocols: Updates from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv. 2019;93(7):ccd.28307. doi:10.1002/ccd.28307 Doll JA, Ohman EM, Patel MR, et al. A team-based approach to patients in cardiogenic shock. Catheter Cardiovasc Interv. 2016;88(3):424-433. doi:10.1002/ccd.26297 Thiele H, Ohman EM, de Waha-Thiele S, Zeymer U, Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019. Eur Heart J. 2019;40(32):2671-2683. doi:10.1093/eurheartj/ehz363 Thiele H, Akin I, Sandri M, et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017;377(25):2419-2432. http://www.nejm.org/doi/10.1056/NEJMoa1710261. Accessed April 10, 2021. Van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement from the American Heart Association. Circulation. 2017;136(16):e232-e268. doi:10.1161/CIR.0000000000000525 Henry, Timothy D., et al. “Invasive Management of Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Scientific Statement from the American Heart Association.” Circulation, vol. 143, no. 15, 2021, doi: 10.1161/cir.0000000000000959. Guest Profiles Dr. Venu Menon Dr. Venu Menon earned his medical degree from Jawaharlal Institute of Postgraduate Medical Education and Research in Pondicherry, India. He completed his internship and residency in internal medicine at St. Luke’s-Roosevelt Hospital in New York, NY, where he served as a Chief Resident. He continued at St. Luke’s-Roosevelt for his Cardovascular fellowship. Dr. Menon is currently the Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine. He serves as the section head of clinical cardiology, fellowship program director, and director of the Cardiac intensive care unit at the Cleveland Clinic. He is the Chair of the AHA’s Acute Cardiac Care and General Cardiology Committee of the Council on Clinical Cardiology. Dr. Priya Kothapalli Dr. Priya Kothapalli completed her medical school at Temple University. She did her residency at Houston Methodist. She is currently the chief fellow and CardioNerds ambassador at University of Texas at Austin, and will soon become the institution’s first ever interventional cardiology fellow CardioNerds Cardiac Critical Care Production Team Karan Desai, MD Dr. Mark Belkin Dr. Yoav Karpenshif Amit Goyal, MD Daniel Ambinder, MD

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