Cardionerds: A Cardiology Podcast

CardioNerds cofounders Dr. Amit Goyal and Dr. Daniel Ambinder join Dr. Isabel Balachandran, Dr. Diego Celli from the Texas Heart Institute. They discuss the nuances of risk stratification management of intermediate risk pulmonary embolism. The ECPR for this episode was provided by Dr. Alam Mahboob (Associate Professor of Medicine at Baylor College of Medicine and the Department of Medicine and Associate Program Director for the Cardiovascular Disease Fellowship Program at Baylor). Audio editing by CardioNerds Academy Intern, Dr. Chelsea Amo Tweneboah. “To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. 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 – Caring for the Middle Child of Pulmonary Embolism – Texas Heart Institute Pearls – Caring for the Middle Child of Pulmonary Embolism – Texas Heart Institute Submassive pulmonary embolism is defined as an intermediate risk group of acute pulmonary embolism, which presents with signs of RV dysfunction and myocardial injury without hemodynamic instability. The AHA, ACCP, and ESC have variable definitions of submassive PE. Non-invasive tools such as EKG, TTE, and CT are critical to defining RV dysfunction. The Pulmonary Embolism Severity Index (PESI) score is a validated tool to help risk stratify patients with PE. Advanced therapies for submassive PE include systemic thrombolysis, catheter-based intervention, surgical embolectomy, and mechanical circulatory support. The decision between these therapies is based on individual patient risk profiles, local expertise, and the risk of major bleeding. There is a spectrum of long-term complications after an acute PE, ranging from post PE syndrome to CTEPH (chronic thromboembolic pulmonary hypertension) caused by a maladaptive vascular remodeling from residual thrombus or arteriopathy. Thrombolytic therapies are still controversial in reducing the risk of post PE complications. PERT is a multidisciplinary group of clinicians who can rapidly assess and triage patients with acute PE, coordinate access to medical and advanced therapies, and provide the necessary follow up care. Show Notes – Caring for the Middle Child of Pulmonary Embolism – Texas Heart Institute How do you define “submassive” pulmonary embolism? Venous thromboembolism, which includes deep vein thrombosis and acute pulmonary emboli (PE) are the third most common cardiovascular disorder in the United States with approximately 900,000 cases occurring each year (1). The morbidity and mortality associated with pulmonary emboli are also great, with approximately 33% of PE cases being fatal (1). Until recently, PE was previously classified into massive or non-massive. Massive PE was defined as those with cardiogenic shock. A newer group, “submassive PE”, was defined as an “intermediate” risk group. According to the American Heart Association (AHA) Scientific Statement on the management of massive and submassive PE, patients in this group presented with signs of RV dysfunction and myocardial necrosis without hemodynamic instability (2). Intermediate-risk PE covers a broad range of risk and management decisions remain challenging. Intermediate-risk PE convers increased risk for mortality and complications compared with low-risk PE.  How do you risk-stratify intermediate-risk pulmonary emboli? The AHA, American College of Chest Physicians (ACCP), and European Society of Cardiology (ESC) have variable definitions of submassive PE and which biomarkers should be used (1,3). The contents are summarized as below (Table 1) Each major guideline highlights the importance of the evaluation of RV dysfunction (RVD) and elevated biomarkers. To summarize, the AHA defines submassive PE with either RVD or elevated biomarkers, specifically troponin levels (2). The ACCP similarly defines an intermediate risk PE with either RVD or elevated biomarkers, though with both elevated BNP/NT-proBNP or troponin levels (4). Finally, the ESC subdivides intermediate risk into intermediate-high and intermediate-low risk groups based on the PESI score and if there are elevated troponin levels (3). As of 2019, the AHA published a consensus statement revising the nomenclature of PE. The terminology is now high risk, intermediate risk, and low risk (4).  The AHA 2011 guidelines define RVD based on the following non-invasive tools (EKG, CT and transthoracic echocardiography) (2).By EKG, concerning changes include a new or incomplete right bundle branch block, anteroseptal ST elevation or depression, or anteroseptal T wave inversions. Other pertinent findings include sinus tachycardia (the most common abnormality), atrial arrhythmias, low voltages, right axis deviation, S1Q3T3, or Qr pattern in V1 (2).By CT, RV enlargement is defined as an RV to LV diameter ratio > 0.90 (2).By TTE, RV enlargement (RV to LV diameter ratio > 0.9), systolic dysfunction (TAPSE <17 mm or S’ <0.1 m/s) or hypokinesis (sometimes with the preservation of apical contractility- aka McConnell’s sign) (2). There can also be signs of pulmonary hypertension, which include flattening of the interventricular septum during systole or a tricuspid regurgitant velocity > 2.7 m /sec. Finally, there can also be direct visualization of thrombus within the right sided chambers (5). The PESI or Pulmonary Embolism Severity Index is a validated tool using markers such as age, sex, vital signs, presence of hypoxemia, altered mental status, and comorbidities (such as cancer, heart failure, and chronic lung disease) to risk stratify patients with PE. A high PESI score is suggestive of an elevated 30-day mortality (6). What is the general approach to therapeutic interventions and treatment for submassive PE? With confirmed PE and no contraindications to systemic anticoagulation prompt use of low molecular weight heparin (LMWH), unfractionated heparin, or fondaparinux should be used. For those confirmed with heparin induced thrombocytopenia, a non-heparin based anticoagulant (such as argatroban or bivalirudin) should be used (2). In regards to direct oral anticoagulation (DOAC), in large studies (including the EINSTEIN and AMPLIFY trials), patients with submassive PE predominantly received LMWH prior to DOAC initiation. It is uncertain whether direct initiation of DOAC is comparable in outcomes (1). Treatment with systemic anticoagulation alone in normotensive patients with RV dysfunction, is controversial and the use of more aggressive therapies has been studied extensively. Advanced therapies for submassive PE include systemic thrombolysis, catheter-based interventions, surgical embolectomy, and mechanical circulatory support. The decision between these therapies is based on individual patient risk as well as the risk of major bleeding, best guided by pulmonary embolism response teams (PERT) (7). Finally, surgical embolectomy is considered in those with submassive and massive PE in whom fibrinolytic therapy has failed or is contraindicated. Other indications include paradoxical emboli, clot in transit, or hemodynamic collapse. In large, high-volume centers, this has been found to be a safe and effective approach (1). Hemodynamic support is important to consider for management of RV failure. If a limited intravenous fluid trial fails, early vasopressor and inotropic support should be initiated. ECMO is indicated for hemodynamic and ventilatory support in patients with severe RV failure and refractory cardiogenic shock (7). When do you consider systemic thrombolysis or catheter directed therapies for patients with intermediate-risk PE? Systemic thrombolysis works by rapidly acting on acute thrombus, thereby reducing pulmonary pressures and RV dysfunction, along with improving hemodynamics. This has been shown to be superior to anticoagulation alone in massive PE with reductions in mortality at the cost of increased major bleeding (1,2). The PEITHO trial was the largest randomized control trial of systemic thrombolysis in PE. Thrombolytic treatment with Tenecteplase reduced a composite outcome of all-cause mortality at 7 days and hemodynamic decompensation versus anticoagulation with heparin alone. This, however, came at the expense of an increased risk of major bleeding (including intracranial hemorrhage) (8). Given this concern, the MOPPET-3 trial in 2013 evaluated the effect of low dose thrombolysis on outcomes in patients with submassive PE. It was found that low dose tPA reduced the incidence of pulmonary hypertension. However, tPA did not reduce the rates of a combined outcome of recurrent PE or all-cause mortality (9). Catheter-based therapy, including pharmacomechanical therapy, catheter-directed thrombolysis, and mechanical embolectomy, is a widely studied approach for treating pulmonary embolism (PE) (10). In 2013, the ULTIMA trial compared CDT plus anticoagulation versus anticoagulation alone in intermediate-high risk PE and found that CDT resulted in a statistically significant improvement in the right ventricular/left ventricular (RV/LV) ratio at 24 hours. At 90 days, there was no difference in mortality or major bleeding events between the two groups (11). A recent meta-analysis compared CDT to systemic anticoagulation (sAC) alone and showed lower rates of in-hospital, 30-day, and 90-day mortality, with no differences in major or minor bleeding or blood transfusions (10). The most widely studied technique is ultrasound-facilitated catheter-directed fibrinolysis (EKOS), which combines local fibrinolysis with mechanical thrombectomy. The SEATTLE II trial found a reduction in mean RV/LV ratio and mean pulmonary artery systolic pressure at 48 hours post-thrombolysis. Although major bleeding occurred in 10% of patients, there was no intracranial hemorrhage (12). The OPTALYSE trial aimed to determine the optimal dose of tissue plasminogen activator (TPA) and found that a lower dose delivered over a shorter duration resulted in improved right ventricular function and reduced clot burden compared to baseline (13). In contrast, the SUNSET trial failed to demonstrate better outcomes or safety profile between CDT and systemic anticoagulation (14). Pure mechanical catheter thrombectomy, such as the FlowTriever system, can be used in patients with contraindications to fibrinolysis and has been shown to result in a 25% reduction in RV/LV ratio in submassive PE in a multicenter study. However, there is still a lack of significant mortality data or large randomized controlled trials for catheter-based therapy (15). What are common complications after submassive pulmonary emboli? There is a spectrum of long-term complications after an acute PE (including intermediate risk PE), called Post-PE syndrome. These include limitations in functional capacity, cardiopulmonary dysfunction, and an overall decreased quality of life. In addition, chronic thromboembolic pulmonary disease (CTEPH) can occur which is characterized by persistent pulmonary vasoconstriction and arterial obstruction (16). The pathophysiology behind these complications are likely due to maladaptive vascular remodeling from residual thrombus or arteriopathy which results in increased pulmonary vascular resistance and possibly further RV dysfunction (17). In the ELOPE study, a prospective cohort study, almost half of acute PE patients had exercise limitations at 1 year on cardiopulmonary exercise testing, based on a VO2-max <80% predicted (18). Further, another study found that approximately 45% to 52% of surviving PE patients exhibit a New York Heart Association Score of ≥2 even up to 3 years after the acute incident (19). The evidence for thrombolytics is still controversial with regards to impact on long term outcomes. Though the PEITHO study has the largest long term follow up of advanced therapies and thrombolysis, there was no significant reduction in chronic PE complications, RV dysfunction, or persistent symptoms with thrombolysis (1,2). However, several smaller studies have now reported long term benefits of thrombolysis (TOPCOAT and MOPPET trial) with improved functional outcomes and quality of life (2). What is a PERT team and what is their role in the management of pulmonary emboli? A PERT or pulmonary embolism response team brings together a multidisciplinary group of clinicians who can rapidly assess and provide treatments for acute PE, who can exercise a full range of medical, endovascular, and surgical therapies, and who can provide appropriate follow up for patients (2, 17). PERT teams’ structures are variable based on the institution and the optimal PERT structure is not fully known. Often, however, a team will include emergency medicine, critical care, non-invasive and interventional cardiology, vascular medicine, vascular surgery, hematology, cardiac surgery, and clinical pharmacy.  To date, there are officially 89 institutions who are a part of the PERT consortium (17). PERT are useful in the decision making of not only submassive or massive PE, but also low risk PE with complex comorbidities. Though there has not been a formal randomized controlled trial to evaluate the PERT approach for survival, complications, and cost effectiveness, there have been several retrospective and prospective studies that have addressed these questions. Overall, PERT allows earlier access to advanced therapies, a streamlined approach to facilitate multidisciplinary communication, and an ability to quickly mobilize resources. There has been a proportional increase in the utilization of advanced therapies based on descriptive studies (from 9-19% in one study) without a significant increase in bleeding complications or mortality (20). One interesting development is the incorporation of AI. AI is at the forefront of cardiovascular care now, and this includes PE management. There are AI powered PE care coordination software (Viz AI for example), which have been useful in resource limited settings. Alerts are provided to the team with relevant clinical information and even automated imaging analysis (21). Though bringing together multiple perspectives can be helpful, it is also resource intensive that requires infrastructure. Future research is needed also in the costs associated with developing and maintaining a team. Outpatient follow up is additionally an important area for growth, specifically with post procedural care, medication adherence, and age appropriate cancer screening (2). References Nguyen, P. C., Stevens, H., Peter, K., & McFadyen, J. D. (2021). Submassive pulmonary embolism: current perspectives and future directions. Journal of Clinical Medicine, 10(15), 3383.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347177/#:~:text=What%20Is%20the%20Definition%20of,%2C%20and%20standard%2Drisk%20PE. Jaff, M. R., McMurtry, M. S., Archer, S. L., Cushman, M., Goldenberg, N., Goldhaber, S. Z., … & Zierler, B. K. (2011). Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation, 123(16), 1788-1830. https://www.ahajournals.org/doi/10.1161/cir.0b013e318214914f#d1e2825 Konstantinides, S. V., Meyer, G., Becattini, C., Bueno, H., Geersing, G. J., Harjola, V. P., … & Zamorano, J. L. (2020). 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European heart journal, 41(4), 543-603. https://academic.oup.com/eurheartj/article/41/4/543/5556136 Chodakowski, J. D., & Courtney, D. M. (2018). Pulmonary embolism critical care update: prognosis, treatment, and research gaps. Current opinion in critical care, 24(6), 540-546. https://journals.lww.com/co-criticalcare/Abstract/2018/12000/Pulmonary_embolism_critical_care_update_.18.aspx Ronny, C., Pablo, L., Victor, N., & Brooks, M. (2012). Echocardiographic findings in pulmonary embolism: An important guide for the management of the patient. World Journal of Cardiovascular Diseases, 2012. DOI:10.4236/wjcd.2012.23027 Mattia Arrigo, Lars Christian Huber, Pulmonary Embolism and Heart Failure: A Reappraisal, Cardiac Failure Review 2021;7:e03. https://doi.org/10.15420/cfr.2020.26 Piazza, G. (2020). Advanced management of intermediate-and high-risk pulmonary embolism: JACC focus seminar. Journal of the American College of Cardiology, 76(18), 2117-2127. https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.05.028 Meyer G, et al. “Fibrinolysis for patients with intermediate-risk pulmonary embolism”. The New England Journal of Medicine. 2014. 370(15):1402-1411. https://www.nejm.org/doi/full/10.1056/NEJMoa1302097 Sharifi M, et al. “Moderate pulmonary embolism treated with thrombolysis”. The American Journal of Cardiology. 2013. 111(2):273-277. https://www.sciencedirect.com/science/article/abs/pii/S0002914912022059 Pei, D. T., Liu, J., Yaqoob, M., Ahmad, W., Bandeali, S. S., Hamzeh, I. R., … & Alam, M. (2019). Meta-analysis of catheter directed ultrasound-assisted thrombolysis in pulmonary embolism. The American journal of cardiology, 124(9), 1470-1477. https://www.sciencedirect.com/science/article/abs/pii/S0002914919308707 Kucher, N., Boekstegers, P., Müller, O. J., Kupatt, C., Beyer-Westendorf, J., Heitzer, T., … & Baumgartner, I. (2014). Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation, 129(4), 479-486. https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.113.005544 Piazza, G., Hohlfelder, B., Jaff, M. R., Ouriel, K., Engelhardt, T. C., Sterling, K. M., … & SEATTLE II Investigators. (2015). A prospective, single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II study. Cardiovascular Interventions, 8(10), 1382-1392. https://www.jacc.org/doi/abs/10.1016/j.jcin.2015.04.020 Tapson, V. F., Sterling, K., Jones, N., Elder, M., Tripathy, U., Brower, J., … & Goldhaber, S. Z. (2018). A randomized trial of the optimum duration of acoustic pulse thrombolysis procedure in acute intermediate-risk pulmonary embolism: the OPTALYSE PE trial. JACC: Cardiovascular Interventions, 11(14), 1401-1410. https://www.jacc.org/doi/abs/10.1016/j.jcin.2018.04.008 Avgerinos, E. D., Jaber, W., Lacomis, J., Markel, K., McDaniel, M., Rivera-Lebron, B. N., … & Chaer, R. (2021). Randomized trial comparing standard versus ultrasound-assisted thrombolysis for submassive pulmonary embolism: the SUNSET sPE trial. Cardiovascular Interventions, 14(12), 1364-1373. https://www.jacc.org/doi/abs/10.1016/j.jcin.2021.04.049 Bishay, V. L., Adenikinju, O., & Todd, R. (2021). FlowTriever Retrieval System for the treatment of pulmonary embolism: overview of its safety and efficacy. Expert Review of Medical Devices, 18(11), 1039-1048. https://www.tandfonline.com/doi/abs/10.1080/17434440.2021.1982379 Piazza, G. (2020). Advanced management of intermediate-and high-risk pulmonary embolism: JACC focus seminar. Journal of the American College of Cardiology, 76(18), 2117-2127. https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.05.028 Rosovsky R, Zhao K, Sista A, Rivera-Lebron B, Kabrhel C. Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost. 2019;3(3):315-330. Published 2019 Jun 9. doi:10.1002/rth2.12216. https://www.sciencedirect.com/science/article/pii/S2475037922016181 Kahn SR, Akaberi A, Granton JT, Anderson DR, Wells PS, Rodger MA, et al. Quality of life, dyspnea, and functional exercise capacity following a first episode of pulmonary embolism: results of the ELOPE cohort study. Am J Med. 2017;130:990 e9–e21. [PubMed] Stevinson BG, Hernandez‐Nino J, Rose G, Kline JA. Echocardiographic and functional cardiopulmonary problems 6 months after first‐time pulmonary embolism in previously healthy patients. Eur Heart J. 2007;28:2517–24. https://academic.oup.com/eurheartj/article/28/20/2517/415870  Rosovsky R, Chang Y, Rosenfield K, Channick R, Jaff MR, Weinberg I, et al. Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10‐year analysis. J Thromb Thrombolysis. 2018;47:31-40. [PubMed] ) 

CardioNerds cofounder Dr. Daniel Ambinder, series co-chair Dr. Dinu Balanescu (FIT, Mayo Clinic), and episode lead Dr. Anjali Rao (FIT, UTSW) discuss training in cardio-oncology with Dr. Stephanie Feldman from Rutgers University. In this episode, the group discusses some of the most burning questions about educating the next wave of cardio-oncologists. As Dr. Feldman mentions, the projected number of cancer survivors is predicted to be around 24 million by 2024, underscoring the growing importance of cardio-oncology in our practice. We highlight some of the challenges facing trainees and training programs alike, including how to integrate cardio-oncology education into general cardiology training, the optimal structure for an advanced cardio-oncology fellowship, and the role of cardio-oncology in the inpatient setting. We also talk about the takeaways from the ACC Cardio-Oncology Leadership Council document. Dr. Feldman reflects on the importance of flexibility in education in the current landscape, drawing on her personal experience as a cardio-oncologist during the COVID-19 era. Notes were drafted by Dr. Anjali Rao. Audio editing was performed by student doctor, Shivani Reddy. This episode is supported by a grant from Pfizer Inc. This CardioNerds Cardio-Oncology 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. Giselle Suero Abreu, Dr. Dinu Balanescu, and Dr. Teodora Donisan.  Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Pearls • Notes • References • Production Team CardioNerds Cardio-Oncology 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 – Cardio-Oncology: Training and Future Directions It may be possible to achieve “COCATS level 2” cardio-oncology training during general cardiology fellowship. A dedicated cardio-oncology year may appeal to trainees who want to achieve “COCATS level 3”, i.e., dedicate their practice to caring for patients with complex cardio-oncology needs, become involved in clinical trials, and lead cardio-oncology clinical and training programs. Supplemental learning opportunities for general fellows can include: Rotating in a cardio-oncology clinic, ideally attached to a National Cancer Institute-designated cancer center Multi-modality cardiac imaging Participating in cardio-oncology research Some currently available educational opportunities include: The International Cardio-Oncology Society (ICOS) weekly webinars The American Society of Echocardiography (ASE) webinars on global longitudinal strain The American Society of Nuclear Cardiology lecture series on cardiac amyloidosis Cardio-oncology focused conferences, such as the American College of Cardiology’s (ACC) Advancing the Cardiovascular Care of the Oncology Patient and Memorial Sloan Kettering’s Cardio-Oncology Symposium. Each institution may have different inpatient cardio-oncology needs depending on whether there is a stand-alone cancer hospital or another format. Examples of inpatient consults that may benefit from having a cardio-oncologist involved include: Cardiovascular risk assessment prior to bone marrow transplant or cancer related surgery in a patient with known coronary artery disease Immune checkpoint inhibitor myocarditis Chemotherapy-related cardiac dysfunction Management of systemic anticoagulation in a patient with high CHA2DS2-VASc and chemotherapy related thrombocytopenia. Show notes – Cardio-Oncology: Training and Future Directions The need for cardio-oncology experience is undeniable given the growing population of patients with cancer and cardiovascular disease, particularly given the number of anti-neoplastic therapies with potential cardiovascular side effects. There are several strategies for incorporating cardio-oncology experiences into general cardiology training. These may include rotating through a cardio-oncology clinic, enhanced exposure to multimodality cardiac imaging including global longitudinal strain and participating in cardio-oncology research. The need for dedicated formal training in cardio-oncology is more nuanced. If the goals of a formal fellowship align with a trainee’s career goals, an additional year of training can provide advanced exposure to complex medical decision-making, cardio-oncology specific imaging training (i.e., global longitudinal strain, MRI, PET), and even inpatient cardio-oncology experience at several centers. Prospective cardio-oncology trainees should gain clinical exposure during general cardiology fellowship and research exposure where available, and these experiences can factor into their decision to pursue a cardio-oncology fellowship. Additional resources from national societies (e.g., ICOS, ACC, ASE) for cardio-oncology education can be made available to general cardiology trainees to expand their knowledge base. In some institutions, inpatient cardio-oncology consults may be appropriate. As a general rule, consultations regarding chemo- or immunotherapy-related cardiotoxicities or pre-stem cell transplant risk stratification may benefit from involvement of cardio-oncology in some form. The future of cardio-oncology is bright, especially with the development of programs to train the next generation of cardio-oncologists! References – Cardio-Oncology: Training and Future Directions Tuzovic M, Brown SA, Yang EH, et al. Implementation of Cardio-Oncology Training for Cardiology Fellows. JACC CardioOncol. 2020;2(5):795-799. Published 2020 Dec 15. · CardioOncology Education and Training. Alvarez-Cardona JA, Ray J, Carver J, et al. Cardio-Oncology Education and Training: JACC Council Perspectives. J Am Coll Cardiol. 2020;76(19):2267-2281. Cardio-oncology Training in the COVID-19 Era. Feldman S, Liu J, Steingart R, Gupta D. Cardio-oncology Training in the COVID-19 Era. Curr Treat Options Oncol. 2021;22(7):58. Published 2021 Jun 7. Meet Our Collaborators International Cardio-Oncology Society ( IC-OS). IC-OS exits to advance cardiovascular care of cancer patients and survivors by promoting collaboration among researchers, educators and clinicians around the world. Learn more at https://ic-os.org/.

The following question refers to Section 6.1 of the 2021 ESC CV Prevention Guidelines. The question is asked by MGH internal medicine resident Dr. Christian Faaborg-Andersen, answered first by UCSD early career preventive cardiologist Dr. Harpreet Bhatia, and then by expert faculty Dr. Eugenia Gianos. Dr. Gianos specializes in preventive cardiology, lipidology, cardiovascular imaging, and women’s heart disease; she is the Director of Women’s Heart Health at Lenox Hill Hospital and Director of Cardiovascular Prevention for Northwell Health. 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. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #30 A 65-year-old woman with a history of hypertension, type 2 diabetes mellitus, and coronary artery disease with remote PCI to the RCA presents for follow-up. She has stable angina symptoms that are well controlled with metoprolol tartrate 25 mg BID and are not lifestyle limiting. She takes aspirin 81 mg daily and atorvastatin 40 mg daily. Her LDL-C is 70 mg/dL, hemoglobin A1c is 7.0%, and eGFR is >60. In clinic, her BP is 118/80 mmHg. What is the next step in management? A Increase atorvastatin for goal LDL-C < 55 mg/dL B No change in management C Add isosorbide mononitrate 30 mg daily D Stop aspirin E Start a sulfonylurea Answer #30 Explanation   The correct answer is A – increase atorvastatin for goal LDL-C < 55 mg/dL. In patients with established ASCVD, the ESC guidelines advocate for an LDL goal of < 55 mg/dL with at least a 50% reduction from baseline levels (Class I, LOE A). This patient has stable angina which is not lifestyle limiting; as such, further anti-anginal therapy is not necessary. She has known CAD with prior PCI, so aspirin therapy is appropriate for secondary prevention (Class I, LOE A). There is no indication for a sulfonylurea as her diabetes is well controlled. Notably, in persons with type 2 DM and ASCVD, the use of a GLP-1RA or SGLT2 inhibitor with proven outcome benefits is recommended to reduce CV and/or cardiorenal outcomes (Class I, LOE A). Main Takeaway For people with established ASCVD, the ESC-recommended LDL-C goal is < 55 mg/dL with a goal reduction of at least 50%. Guideline Loc. Section 6.1 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 Sections 10.2 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Western Michigan University medical student and CardioNerds Intern Shivani Reddy, answered first by Mayo Clinic Cardiology Fellow and CardioNerds Academy House Faculty Leader Dr. Dinu Balanescu, and then by expert faculty Dr. Ileana Pina. Dr. Pina is Professor of Medicine and Quality Officer for the Cardiovascular Line at Thomas Jefferson University, Clinical Professor at Central Michigan University, and Adjunct Professor of Biostats and Epidemiology at Case Western University. She serves as Senior Fellow and Medical Officer at the Food and Drug Administration’s Center for Devices and Radiological Health. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #24 Mr. E. Regular is a 61-year-old man with a history of HFrEF due to non-ischemic cardiomyopathy (latest LVEF 40% after >3 months of optimized GDMT) and persistent atrial fibrillation. He has no other medical history. He has been on metoprolol and apixaban and has also undergone multiple electrical cardioversions and catheter ablations for atrial fibrillation but remains symptomatic with poorly controlled rates. His blood pressure is 105/65 mm Hg. HbA1c is 5.4%. Which of the following is a reasonable next step in the management of his atrial fibrillation? A Anti-arrhythmic drug therapy with amiodarone. Stop apixaban. B Repeat catheter ablation for atrial fibrillation. Stop apixaban. C AV nodal ablation and RV pacing. Shared decision-making regarding anticoagulation. D AV nodal ablation and CRT device. Shared decision-making regarding anticoagulation. Answer #24 Explanation The correct answer is D – AV nodal ablation and CRT device along with shared decision-making regarding anticoagulation.” Maintaining sinus rhythm and atrial-ventricular synchrony is helpful in patients with heart failure given the hemodynamic benefits of atrial systole for diastolic filling and having a regularized rhythm. Recent randomized controlled trials suggest that catheter-based rhythm control strategies are superior to rate control and chemical rhythm control strategies with regards to outcomes in atrial fibrillation. For patients with heart failure and symptoms caused by atrial fibrillation, ablation is reasonable to improve symptoms and quality of life (Class 2a, LOE B-R). However, Mr. Regular has already had multiple failed attempts at ablations (option B). For patients with AF and LVEF ≤50%, if a rhythm control strategy fails or is not desired, and ventricular rates remain rapid despite medical therapy, atrioventricular nodal ablation with implantation of a CRT device is reasonable (Class 2a, LOE B-R). The PAVE and BLOCK-HF trials suggested improved outcomes with CRT devices in these patients. RV pacing following AV nodal ablation has also been shown to improve outcomes in patients with atrial fibrillation refractory to other rhythm control strategies. In patients with EF >50%, there is no evidence to suggest that CRT is more beneficial compared to RV-only pacing. However, RV pacing may produce ventricular dyssynchrony and when compared to CRT in those with reduced EF (≤ 50%), CRT produced more benefit (Option C). Although adjustments in antiarrhythmic medications and repeat ablation may be considered, these are unlikely to provide long-term benefit to Mr. E. Regular, who already failed antiarrhythmic regimens and multiple attempts at cardioversion and ablation (Options A, B). In patients with chronic heart failure and atrial fibrillation, the decision to use anticoagulation for the prevention of cerebrovascular events is generally based on the CHA2DS2-VASc score. Mr. Regular’s CHA2DS2-VASc score is 1 (+1 for HF, no points for: hypertension, age 65-74 or ≥75, diabetes, stroke/TIA/TE, vascular disease, female gender). Chronic anticoagulation therapy is recommended for patients with CHA2DS2-VASc scores ≥2 for men and ≥3 for women (Class 1, LOE A). Therefore, based on the CHA2DS2-VASc score alone, Mr. Regular would not necessarily warrant anticoagulation. However, HF is a hypercoagulable state and serves as an independent risk factor for stroke, systemic embolism, and mortality in the setting of AF. In patients with HF and a CHA2DS2-VASc score of 1, those with AF had a 3-fold higher risk compared with individuals without concomitant AF. Because HF is a risk factor, additional risk factors may not be required to support the use of anticoagulation in patients with HF, and the decision to anticoagulate can be individualized according to risk versus benefit. The guidelines give a Class 2a recommendation for chronic anticoagulation in men and women with chronic HF and permanent-persistent-paroxysmal AF who have no additional risk factors (LOE B-NR). Therefore, decisions regarding anticoagulation in this context should incorporate patient values, comorbidities, and informed shared decision making.   Main Takeaway In summary, the “ablate and pace” strategy of AV nodal ablation and CRT device implantation improve outcomes in patients with heart failure with reduced LVEF and atrial fibrillation refractory to chemical and catheter-based rhythm control strategies and failure of rate control options. Guideline Loc. Section 10.2 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

In this episode, CardioNerds co-founder Amit Goyal joins Dr. Iva Minga, Dr. Kevin Lee, and Dr. Juan Pablo Salazar Adum from the University of Chicago – Northshore in Evanston, IL to discuss a case of primary cardiac diffuse large B-cell lymphoma. The ECPR for this episode is provided by Dr. Amit Pursnani (Advanced Cardiac Imaging, Fellowship program director, NorthShore University HealthSystem). Audio editing by CardioNerds Academy Intern, Dr. Akiva Rosenzveig. Case synopsis: A 77-year-old man with no significant medical history presents to the emergency department with progressive shortness of breath for 1 week. He reports an unintentional 15-pound weight loss in the prior month as well as constipation and abdominal/flank pain. On examination he was found to be tachycardic with a regular rhythm and further evaluation with a chest X-ray and chest CT scan demonstrated a large pericardial effusion. This was further investigated with an urgent echocardiogram that revealed a large pericardial effusion with a large mass attached to the pericardial side of the RV free wall, as well as signs of early cardiac tamponade. A pericardiocentesis was performed and 550mL of bloody fluid was withdrawn. The fluid was sent for laboratory analysis and cytology. A cardiac MRI demonstrated a large invasive mass in the pericardium and RV wall consistent with cardiac lymphoma. Cytology confirmed diffuse large B-cell lymphoma. Subsequent CT and PET scans did not find any other site of malignancy, giving the patient a diagnosis of primary cardiac diffuse large B-cell lymphoma. The patient underwent R-CHOP chemotherapy and was followed closely with repeat cardiac MRI and PET scans which demonstrated resolution of the cardiac mass at his one-year surveillance follow-up. This case was published in US Cardiology Review, the official journal of CardioNerds. To learn more, access the case report article here. “To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine. CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ). Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. 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! Pearls – A Mystery Mass in the Heart – Cardiac Lymphoma The most common cause of malignant cardiac masses is metastasis. Primary cardiac tumors are rare. Cardiac tumors are separated into 2 categories: benign and malignant. They are often differentiated based on their location and their degree of tissue invasion. Multimodality imaging is essential in the diagnosis, management, and surveillance of cardiac masses. A multidisciplinary team approach is invaluable for management of patients with cardiac tumors. Show Notes – A Mystery Mass in the Heart – Cardiac Lymphoma 1. What is the clinical presentation of cardiac masses? Cardiac masses can have a variable presentation. They can present with arrhythmias, angina, heart failure symptoms, or pericardial effusion. Patients can also be asymptomatic; the masses can be found incidentally on cardiac or chest imagining. 2. What is the differential diagnosis for cardiac masses? Cardiac masses are separated into benign and malignant. The most common malignant cardiac masses are metastases from a distant source. The location of the mass is important in narrowing the differential. 3. What imaging modalities are used to diagnose cardiac masses? Multimodality imaging is needed to describe the mass in detail and guide diagnosis. An echocardiogram is usually the first imaging modality. Cardiac MRI is a great modality that allows for the detailed visualization as well as tissue characterization of the mass. Cardiac CT, chest CT, and PET scans are also imagining modalities that can be used in the management of the mass. 4. How do you manage cardiac masses? Management of cardiac masses depends on etiology (benign or malignant) and the associated hemodynamic changes associated with it. For example, if a benign cardiac mass is associated with significant valvular regurgitation, cardiac surgery needs to be considered for management. A multidisciplinary team including cardiology, heart failure, critical care cardiology, cardio-oncology, oncology, cardiac surgery, and other specialties may be involved in the management of cardiac masses and their manifestations. References – A Mystery Mass in the Heart – Cardiac Lymphoma 1. Alerhand, S., & Carter, J. (2019). What echocardiographic findings suggest a pericardial effusion is causing tamponade? American Journal of Emergency Medicine, 37(2), 321-326. 2. McAllister, H. A., & Fenoglio, J. J. (1978). Tumors of the Cardiovascular System. Atlas of Tumor Pathology, Series 2. Armed Forces Institute of Pathology, Washington DC, 2, 20. 3. Tyebally, S., Chen, D., Bhattacharyya, S., Mughrabi, A., Hussain, Z., Manisty, C., Westwood, M., Ghosh, A. K., & Guha, A. (2020). Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC. CardioOncology, 2(2), 293-311. 4. Motwani, M., Kidambi, A., Herzog, B. A., Uddin, A., Greenwood, J. P., & Plein, S. (2013). MR imaging of cardiac tumors and masses: a review of methods and clinical applications. Radiology, 268(1), 26-43. 5. Spodick, D. H. (2003). Acute cardiac tamponade. New England Journal of Medicine, 349(7), 684-690.

In this episode, Dr. Gurleen Kaur (medicine resident at Brigham and Women’s Hospital and Director of CardioNerds Internship) and CardioNerds Academy interns Dr. Akiva Rosenzveig (medicine intern at Cleveland Clinic), Dr. Chelsea Tweneboah (medicine intern at Stonybrook University), student doctor Shivani Reddy (medical student at Western Michigan University), student doctor Diane Masket (medical student at Rowan School of Osteopathic Medicine), and student doctor Tina Reddy (medical student at Tulane University School of Medicine) discuss with Dr. Michelle Kittleson (Director of Education in Heart Failure and Transplantation, Director of HF Research, and Professor of Medicine at Cedars Sinai) about Mastering the Art of Patient Care. Dr. Kittleson shares pearls of wisdom from her book on topics including career transitions, mentorship, dealing with uncertainty, learning from mistakes, delivering difficult news, and being a woman and parent in medicine.   This episode was planned by Dr. Gurleen Kaur and episode audio was edited by student doctor Tina Reddy. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

Dr. Amit Goyal (CardioNerds co-founder), Dr. Jessie Holtzman (House Faculty in CardioNerds Academy and cardiology fellow at UCSF), and Dr. Megan McLaughlin (CardioNerds Scholar and cardiology fellow at UCSF) discuss stimulant-associated cardiomyopathy with Dr. Jonathan Davis (Associate Professor at UCSF the Director of the Heart Failure Program at Zuckerberg San Francisco General Hospital) and Dr. Soraya Azari (Associate Clinical professor at UCSF, with specialty in hospital medicine, primary care, HIV medicine, and addiction medicine).   Methamphetamine-associated heart failure admissions have steadily increased in the United States over the past decade. Substance use disorders more broadly are thought to complicate at least 15% of all heart failure hospitalizations and amphetamine use has been shown to be an independent predictor of heart failure readmission across the country. At safety net and public hospitals, these numbers may rise even higher. This episode reviews the pathophysiology of stimulant associated cardiomyopathy, highlights treatment options for stimulant use disorder, and discusses novel models of co-management of heart failure and substance use disorder.  Notes were drafted by Dr. Jessie Holtzman. Audio editing by CardioNerds academy intern, Pace Wetstein. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Heart Success Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls – Stimulant-Associated Cardiomyopathy Though there are no pathognomonic traits of stimulant-associated cardiomyopathy, common echocardiographic features include biventricular dilated cardiomyopathy and/or pulmonary hypertension with a dilated, hypokinetic right ventricle and underfilled left ventricle. Enjoy CardioNerds Episode 312. Case Report: Life in the Fast Lane Leads to a Cardiac Conundrum to learn from a case of stimulant associated pulmonary arterial hypertension.   Not all cardiomyopathy in patients who use stimulants is due to stimulant use. Do your due diligence. Patients who use stimulants should undergo a broad work-up to diagnose the etiology of cardiomyopathy.   Tips for taking a substance use history:  Ask permission to discuss the topic.  Normalize the behavior.  Use specific drug names (also, learn the local drug nicknames!).  Ask about any history of prior treatment and periods of abstinence.  Screen for risk of harm or overdose   Try using a phrase like “I’m asking you this because I want to know if the way you are using drugs can impact your health and keep you safe.”  There are no FDA-approved medications to treat stimulant use disorder. Common off-label therapies include mirtazapine and bupropion/naltrexone.   Contingency management programs work off the principle of operant conditioning; they reward patients for maintaining abstinence from substance use.   For clinicians to seek assistance in providing treatment for stimulant use disorder, important resources include:   SAMSA (national help line 1-800-662-HELP or online resource locator)  HarmReduction.Org  Never Use Alone hotline (800-484-3731)  Show notes – Stimulant-Associated Cardiomyopathy 1. What are common clinical presentations of stimulant-associated cardiomyopathy?   Stimulants have multifactorial physiologic impacts, due both to pharmacologic properties (adrenergic stimulation and vasoconstriction) and direct toxic effects. Clinical manifestations may include hypertension, tachyarrhythmias, acute myocardial infarction, cardiomyopathy, pulmonary hypertension, aortic dissection, and sudden cardiac death.   On echocardiogram, stimulant-associated cardiomyopathy may manifest as biventricular dilated cardiomyopathy, compensatory tachycardia, LV thrombus, and/or pulmonary hypertension (WHO Group I)  2. What is the pathophysiology of stimulant associated cardiomyopathy?   Though the exact mechanisms driving stimulant-associated cardiomyopathy are unknown, myocardial injury is thought to be related to excess catecholamines and the generation of reactive oxygen species, mitochondrial dysfunction, and the downstream effects of microvascular dysfunction and vasospasm.   Some authors have proposed a two-hit phenomenon whereby stimulant use and vulnerable genetics result in more severe clinical presentations.  3. What are common treatment options for stimulant-associated cardiomyopathy and stimulant use disorder in the presence of cardiovascular disease?   As with heart failure in general, start by ensuring that patients receive appropriate goal-directed medical therapy (GDMT) with an ACEI/ARB/ARNI, beta-blocker, MRA, and SGLTi.   If patients struggle with medication adherence, be sure to address the social determinants of health to allow for improved adherence. For instance, consider using bubble packs to help mitigate polypharmacy.   4. What is the Heart Plus Clinic and how can cardiologists work in an interdisciplinary fashion to address both cardiovascular disease and substance use disorders?  The Heart Plus clinic is a multidisciplinary team that links addiction medicine providers and the cardiovascular teams together. The clinic uses contingency management to incentivize abstinence from substance use and works to address barriers to getting medications, taking medications, and navigating polypharmacy. Results are promising so far, with a pilot study demonstrating less stimulant use, more GDMT use, less urgent care use, and more primary care use, along with greater engagement, continuity, and rapport.    5. How do you take a substance use history?    Ask permission: “Is it ok if I ask you about ***”   Normalize the behavior: “Substance use is common” or “I have a lot of patients struggling with ***”   Use specific names when obtaining a drug use history (not just alcohol, tobacco, “drugs”). Learn the names of drugs in your region.   Try using phrases like “I’m asking you this because I want to know if the way you are using drugs can impact your health and keep you safe.”    Ask about their history of past treatment and periods of abstinence.  Screen for patients at risk of harm and/or overdose due to patterns of use and be sure to prescribe naloxone.  6. What are some useful resources for treating patients with active substance use disorders?  Though there currently no FDA-approved medications to treat stimulant use disorder, common off-label therapies include mirtazapine and bupropion/naltrexone.  Contingency management programs work off the principle of operant conditioning and reward patients for maintaining abstinence from substance use. In contingency management programs, a behavior is chosen that you want to see more frequently, and a reward is given. The reward must be given close to the time of behavior and be of sufficient magnitude to demonstrate the desired effect.    There are many resources to help both clinicians and patients treat substance sue disorders. Resources include the SAMSA national help line (1-800-662-HELP) or online resource locator for clinicians. Patients may also access HarmReduction.Org and the NeverUseAlone hotline (800-484-3731) for harm reduction resources.  References – Stimulant-Associated Cardiomyopathy 1. DesJardin J, Leyde S, Davis J. Weathering the perfect storm: management of heart failure in patients with substance use disorders. Heart. 2021;107(16):1353-4. doi: 10.1136/heartjnl-2021-319103. 2. Kevil CG, Goeders NE, Woolard MD, Bhuiyan MS, Dominic P, Kolluru GK, et al. Methamphetamine Use and Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2019;39(9):1739-46. doi: 10.1161/ATVBAHA.119.312461. 3. Kolaitis NA, Saggar R, De Marco T. Methamphetamine-associated pulmonary arterial hypertension. Curr Opin Pulm Med. 2022;28(5):352-60. 4. Leyde S, Abbs E, Suen LW, Martin M, Mitchell A, Davis J, et al. A Mixed-methods Evaluation of an Addiction/Cardiology Pilot Clinic With Contingency Management for Patients With Stimulant-associated Cardiomyopathy. J Addict Med. 2023;17(3):312-8. doi: 10.1097/ADM.0000000000001110. 5. Manja V, Nrusimha A, Gao Y, Sheikh A, McGovern M, Heidenreich PA, et al. Methamphetamine-associated heart failure: a systematic review of observational studies. Heart. 2023;109(3):168-77. doi: 10.1136/heartjnl-2022-321610. 6. Reddy PKV, Ng TMH, Oh EE, Moady G, Elkayam U. Clinical Characteristics and Management of Methamphetamine-Associated Cardiomyopathy: State-of-the-Art Review. J Am Heart Assoc. 2020;9(11):e016704. doi: 10.1161/JAHA.120.016704. https://www.ahajournals.org/doi/epub/10.1161/JAHA.120.016704 

CardioNerds (Drs. Amit Goyal and Dan Ambinder) join Dr. Emily Lee (LAC+USC Internal medicine resident) and Dr. Charlie Lin (LAC+USC Cardiology fellow) as the discuss an important case of stimulant-related (methamphetamine) cardiovascular toxicity that manifested in right ventricular dysfunction due to severe pulmonary hypertension. Dr. Jonathan Davis (Director, Heart Failure Program at Zuckerberg San Francisco General Hospital and Trauma Center) provides the ECPR for this episide. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig. With the ongoing methamphetamine epidemic, the incidence of stimulant-related cardiovascular toxicity continues to grow. We discuss the following case: A 36-year-old man was hospitalized for evaluation of dyspnea and volume overload in the setting of previously untreated, provoked deep venous thrombosis. Transthoracic echocardiogram revealed severe right ventricular dysfunction as well as signs of pressure and volume overload. Computed tomography demonstrated a prominent main pulmonary artery and ruled out pulmonary embolism. Right heart catheterization confirmed the presence of pre-capillary pulmonary arterial hypertension without demonstrable vasoreactivity. He was prescribed sildenafil to begin management of methamphetamine-associated cardiomyopathy and right ventricular dysfunction manifesting as severe pre-capillary pulmonary hypertension. “To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine. CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ). Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. 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 – stimulant-related (methamphetamine) cardiovascular toxicity Pearls – stimulant-related (methamphetamine) cardiovascular toxicity 1. Methamphetamine, and stimulants in general, can have a multitude of effects on the cardiovascular and pulmonary systems. Effects of methamphetamine are thought to be due to catecholamine toxicity with direct effects on cardiac and vascular tissues. Acutely, methamphetamine can cause vascular constriction and vasospasm, while chronic exposure is associated with endothelial damage. Over time, methamphetamine can cause pulmonary hypertension, atherosclerosis, cardiac arrhythmias, and dilated cardiomyopathy. 2. Methamphetamines are the second most commonly misused substances worldwide after opiates. Patients with methamphetamine-associated pulmonary arterial hypertension (PAH) have more severe pulmonary vascular disease, more dilated and dysfunctional right ventricles, and worse prognoses when compared to patients with idiopathic PAH. Additionally, patients with methamphetamine-associated cardiomyopathy and PAH have significantly worse outcomes and prognoses when compared to those with structurally normal hearts without evidence of PAH. Management includes multidisciplinary support, complete cessation of methamphetamine use, and guideline-directed treatment of PAH. 3. The diagnosis of pulmonary hypertension (PH) begins with the history and physical, followed by confirmatory testing using echocardiography and invasive hemodynamics (right heart catheterization). Initial serological evaluation may include routine biochemical, hematologic, endocrine, hepatic, and infectious testing. Though PH is traditionally diagnosed and confirmed in a two-step, echocardiogram-followed-by-catheterization model, other diagnostics often include electrocardiography, blood gas analysis, spirometry, ventilation/perfusion assessment, CT scans, MRIs, and/or genetic testing to evaluate for the myriad of etiologies that may contribute to the development of PH. 4. PH is characterized by remodeling of the pulmonary vasculature and a progressive increase of pulmonary vascular load, often resulting in right ventricular hypertrophy, remodeling, and dysfunction. PH is defined hemodynamically by a mean pulmonary arterial pressure ≥ 20 mmHg at rest when measured by right heart catheterization (RHC). Pre-capillary pulmonary hypertension due to pulmonary vascular disease is further defined by an elevation in pulmonary vascular resistance (PVR) of at least 3 wood units (WU). 5. Medications used to treat pulmonary arterial hypertension fall into four general mechanistic classes: calcium channel blockers, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin receptor agonists. Show Notes – stimulant-related (methamphetamine) cardiovascular toxicity How is pulmonary hypertension diagnosed with right heart catheterization (RHC)? Pulmonary hypertension is defined by mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg at rest. Pulmonary hypertension has three hemodynamic phenotypes – pre-capillary PH, post-capillary PH, and combined pre-/post-capillary PH. Isolated pre-capillary PH is defined by pulmonary vascular resistance (PVR) ≥ 3 woods units and pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg. Isolated post-capillary PH is defined by PVR < 3 woods units and PAWP > 15 mmHg. PVR is calculated by dividing the mean trans-pulmonary gradient (= PAWP – mPAP) by the cardiac output. Characteristics Clinical groups Isolated pre-capillary PH mPAP >20 mmHgPAWP ≤ 15 mmHgPVR ≥ 3 WU WHO 1,3,4, and 5 Isolated post-capillary PH mPAP >20 mmHgPAWP > 15 mmHgPVR < 3 WU WHO 2 and 5 Combined pre- & post-capillary PH mPAP >20 mmHgPAWP > 15 mmHgPVR ≥ 3 WU WHO 2 and 5 Classification of PAH by WHO Groups: WHO Group 1Pulmonary Arterial Hypertension WHO Group 2Pulmonary hypertension due to left sided heart disease WHO Group 3Pulmonary hypertension due to lung disease or hypoxia WHO Group 4Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions WHO Group 5Pulmonary hypertension with multifactorial mechanisms Idiopathic Left ventricular systolic and/or diastolic dysfunction Chronic obstructive pulmonary disease Chronic thromboembolic pulmonary hypertension Hematological Disease (Sickle cell disease) Hereditary Left-sided valvular heart disease Interstitial lung disease Obstruction of the pulmonary circulation by tumor or inflammation Systemic disorders (Sarcoidosis, Langerhans cell granulomatosis) Drug and toxin induced Other mixed restrictive or obstructive lung disease Metabolic disorders (Gaucher’s disease) Associated with connective tissue disease Sleep-disordered breathing Associated with HIV infection Alveolar hypoventilation disorders Associated with portal hypertension Chronic exposure to high altitude Congenital heart disease Schistosomiasis What is vasoreactivity testing? Pulmonary vasoreactivity testing is used to identify patients who may respond favorably to calcium channel blocker (CCB) treatment. Typically, this includes patients with idiopathic pulmonary arterial hypertension, heritable pulmonary arterial hypertension, or substance-related pulmonary arterial hypertension. It is usually performed at the time of RHC. Inhaled nitric oxide (NO) at 10–20 parts per million (ppm) is the standard of care for vasoreactivity testing with alternatives including intravenous adenosine and epoprostenol. A significant response to vasodilator therapy is defined by a reduction of the mean PAP by at least 10 mmHg and concurrent decrement of the absolute value to less than 40 mmHg, without a decrease in cardiac output. Vasoreactive PH should be treated with CCB therapies such as nifedipine, diltiazem, and amlodipine. Vasoreactivity is relatively rare, occurring in 10% or fewer individuals with PH who undergo testing. PH without vasoreactivity of significant response to CCB therapy should be managed with alternative class of medications (see below). What is the medical treatment for PAH? Medication treatment of pulmonary arterial hypertension comes in 4 general categories with the general mechanism is listed: Calcium channel blockers (nifedipine, diltiazem and amlodipine used in high doses) – used in patients with positive vasoreactivity testing. Endothelin receptor antagonists (ambrisentan, bosentan, macitentan) – inhibit binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells, which is enriched in pulmonary vasculature, resulting in vasodilation and subsequent decrease in pulmonary arterial pressure. Phosphodiesterase 5 inhibitors and guanylate cyclase stimulators (sildenafil, tadalafil, riociguat) – ihibition of the cyclic guanosine monophosphate (cGMP) degrading enzyme phosphodiesterase type 5 results in vasodilation through the NO/cGMP pathway in the pulmonary vasculature, which contains substantial amounts of this enzyme. Prostacyclin analogues and prostacyclin receptor agonists (epoprostenol, iloprost, treprostinil, beraprost) – prostacyclin is produced predominantly by endothelial cells and induces potent vasodilation of all vascular beds and patients with PAH have been shown to have a reduction of prostacyclin synthase expression in the pulmonary arteries. References – Ben-Yehuda O, Siecke N. Crystal Methamphetamine: A Drug and Cardiovascular Epidemic. JACC Heart Fail. Mar 2018;6(3):219-221. doi:10.1016/j.jchf.2018.01.004 Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. Feb 2012;141(2):354-362. doi:10.1378/chest.11-0676 Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. Aug 2019;156(2):323-337. doi:10.1016/j.chest.2019.02.004 Chin KM, Channick RN, Rubin LJ. Is methamphetamine use associated with idiopathic pulmonary arterial hypertension? Chest. Dec 2006;130(6):1657-63. doi:10.1378/chest.130.6.1657 Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. Jan 1 2016;37(1):67-119. doi:10.1093/eurheartj/ehv317 Hassoun PM. Pulmonary Arterial Hypertension. N Engl J Med. Dec 16 2021;385(25):2361-2376. doi:10.1056/NEJMra2000348 Hoeper MM, Humbert M, Souza R, et al. A global view of pulmonary hypertension. Lancet Respir Med. Apr 2016;4(4):306-22. doi:10.1016/s2213-2600(15)00543-3 Kevil CG, Goeders NE, Woolard MD, et al. Methamphetamine Use and Cardiovascular Disease. Arterioscler Thromb Vasc Biol. Sep 2019;39(9):1739-1746. doi:10.1161/atvbaha.119.312461 Reddy PKV, Ng TMH, Oh EE, Moady G, Elkayam U. Clinical Characteristics and Management of Methamphetamine-Associated Cardiomyopathy: State-of-the-Art Review. J Am Heart Assoc. Jun 2 2020;9(11):e016704. doi:10.1161/jaha.120.016704 Zhao SX, Kwong C, Swaminathan A, Gohil A, Crawford MH. Clinical Characteristics and Outcome of Methamphetamine-Associated Pulmonary Arterial Hypertension and Dilated Cardiomyopathy. JACC Heart Fail. Mar 2018;6(3):209-218. doi:10.1016/j.jchf.2017.10.006

The following question refers to Section 5.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by MGH medicine resident Dr. Christian Faaborg-Andersen, answered first by Dr. Jessie Holtzman, 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. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #29 What percentage of the European population currently meets the recommended physical activity guidelines (150 minutes moderate-intensity activity weekly or 75 minutes vigorous-intensity activity weekly)? A <10% B 10-25% C 25-50% D 50-75% E >75% Answer #29 Explanation The correct answer is A: <10% of the European population currently meets the recommended physical activity guidelines. The American Heart Association, European Society of Cardiology, and World Health Organization all share the recommendation that adults should engage in 150 minutes per week of moderate-intensity physical activity or 75 minutes per week of vigorous-intensity activity. They recognize that additional health benefits may be garnered from incremental increases to 300 minutes per week of moderate intensity activity or 150 minutes per week of vigorous intensity activity, with a recommendation to include both aerobic and muscular strength training activities. According to the WHO, physical inactivity is the 4th leading cause of death in the world. The statistics regarding physical inactivity are staggering. Recent studies have shown that <10% of the European population meets the minimum recommended levels of physical activity. Similarly, ¼ adults and ¾ adolescents (aged 11-17) do not currently meet the global recommendations for physical activity. The World Health Organization has created a Global Action Plan on Physical Activity 2018-2030 with the goal to achieve a 15% relative reduction in the global prevalence of physical inactivity by 2030. Society level interventions to increase physical activity have been proposed including school-based activity programs, improved accessibility of exercise facilities across the socioeconomic spectrum, and governmental consideration of physical activity when designing cities (i.e. including pedestrian and cycling lanes). Other policy suggestions with varying levels of evidence include focused media campaigns, economic incentives, targeting labeling of physical activity opportunities, and work-place wellness programs. Main Takeaway Despite growing awareness of the health consequences of sedentary behavior, fewer than 10% of adults currently meet the minimum recommended quantity of physical activity. Public health leaders may continue to consider novel legislative initiatives to augment physical activity on a societal level with architectural design and financial incentives. Guideline Loc. Section 5.2 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 9.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Cedars Sinai medicine resident, soon to be Vanderbilt Cardiology Fellow, and CardioNerds Academy Faculty Dr. Breanna Hansen, and then by expert faculty Dr. Anu Lala. Dr. Lala is an advanced heart failure and transplant cardiologist, associate professor of medicine and population health science and policy, Director of Heart Failure Research, and Program Director for the Advanced Heart Failure and Transplant fellowship training program at Mount Sinai. Dr. Lala is Deputy Editor for the Journal of Cardiac Failure. Dr. Lala has been a champion and role model for CardioNerds. She has been a PI mentor for the CardioNerds Clinical Trials Network and continues to serve in the program’s leadership. She is also a faculty mentor for this very 2022 heart failure decipher the guidelines series. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #23 Mrs. Hart is a 63-year-old woman with a history of non-ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 20-25%) presenting with 5 days of worsening dyspnea and orthopnea.   At home, she takes carvedilol 12.5mg BID, sacubitril-valsartan 24-46mg BID, empagliflozin 10mg daily, and furosemide 40mg daily.   On admission, her exam revealed a blood pressure of 111/79 mmHg, HR 80 bpm, and SpO2 94%. Her cardiovascular exam was significant for a regular rate and rhythm with an audible S3, JVD to 13 cm H2O, bilateral lower extremity pitting edema with warm extremities and 2+ pulses throughout.  What initial dose of diuretics would you give her? A Continue home Furosemide 40 mg PO B Start Metolazone 5 mg PO C Start Lasix 100 mg IV D Start Spironolactone Answer #23 Explanation The correct answer is C – start Furosemide 100 mg IV. This is the most appropriate choice because patients with HF admitted with evidence of significant fluid overload should be promptly treated with intravenous loop diuretics to improve symptoms and reduce morbidity (Class 1, LOE B-NR). Intravenous loop diuretic therapy provides the most rapid and effective treatment for signs and symptoms of congestion. Titration of diuretics has been described in multiple recent trials of patients hospitalized with HF, often initiated with at least 2 times the daily home diuretic dose (mg to mg) administered intravenously. Titration to achieve effective diuresis may require doubling of initial doses, adding a thiazide diuretic, or adding an MRA that has diuretic effects in addition to its cardiovascular benefits. Choice A is incorrect as continuing oral loop diuretics is not recommended for acute decongestion. Moreover, Ms. Hart has become congested despite her home, oral diuretic regimen. Choice B and D are incorrect as starting a thiazide diuretic or a mineralocorticoid receptor antagonist are not first-line therapy for acute HF. Rather, in patients hospitalized with HF when diuresis is inadequate to relieve symptoms and signs of congestion, it is reasonable to intensify the diuretic regimen using either: a. higher doses of intravenous loop diuretics; or b. addition of a second diuretic (Class 2a, LOE B-NR). After instituting intravenous loop diuretic therapy, escalating attempts to achieve net diuresis include serial doubling of intravenous loop diuretic doses, which can be done by bolus or infusion, and sequential nephron blockade with addition of a thiazide diuretic, as detailed specifically in the protocol for the diuretic arms of the CARRESS and ROSE trials. MRAs have mild diuretics properties and the addition of MRAs can help with diuresis in addition to significant cardiovascular benefits in patients with HF. For patients hospitalized with HF, therapy with diuretics and other guideline-directed medications should be titrated with a goal to resolve clinical evidence of congestion to reduce symptoms and rehospitalizations (Class 1, LOE B-NR). For patients requiring diuretic treatment during hospitalization for HF, the discharge regimen should include a plan for adjustment of diuretics to decrease rehospitalizations (Class 1, LOE B-NR). Main Takeaway Patients admitted with acute HF should be promptly treated with intravenous loop diuretics. If current level of diuresis becomes inadequate to relieve symptoms and signs of congestion, it is reasonable to intensify the diuretic regimen using either: higher doses of intravenous loop diuretics or addition of a second diuretic (e.g., thiazide or MRA). All patients should have their diuretic regimen updated on discharge. Guideline Loc. Section 9.3 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!