European Heart Journal

Crea, Filippo

doi: 10.1093/eurheartj/ehab576pmid: 34467397

Open in new tabDownload slide Open in new tabDownload slide  For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Issue opens with a joint Special Article entitled ‘Clinician well-being—addressing global needs for improvements in the health care field: a joint opinion from the American College of Cardiology, American Heart Association, European Society of Cardiology, World Heart Federation’ by Laxmi Mehta from the Ohio State University Wexner Medical Center in the USA.1 The authors note that as clinicians, we strive for improved health for our patients; yet, it is increasingly clear that our own well-being is an essential component of the quadruple aim: to improve population health, enhance patient experience, reduce costs, and improve the work life of healthcare workers. Clinician well-being is described as experiencing satisfaction and engagement with work, while also having a feeling of professional fulfilment and a sense of meaning in work. Conversely, burnout is an occupational phenomenon that is defined as emotional exhaustion, depersonalization, and a sense of low personal accomplishment in a perceived stressful work environment. Although burnout is a sign of clinical distress and a barrier to clinician well-being, its absence alone does not confer a state of well-being. Rather, burnout is one of the more extreme negative components along the spectrum of clinician well-being and can co-exist with other common mental conditions (e.g. anxiety and depression). The Issue continues with a focus on thrombosis and antithrombotic treatment. Infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is mainly characterized by fever and respiratory symptoms, with dyspnoea and lung infiltrates in more severe cases. Many patients also present a procoagulant state. In this context, patients with coronavirus disease 2019 (COVID-19) have an increased risk of developing clinically thrombotic complications such as pulmonary embolism (PE). Immunological and inflammatory-related phenomena may play a role in PE development.2–5 In a Clinical Research article entitled ‘Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome’, Òscar Miró from the University of Barcelona in Spain, and colleagues investigated the incidence, risk factors, clinical characteristics, and outcomes of PE in patients with COVID-19 attending emergency departments (EDs), before hospitalization.6 The authors retrospectively reviewed all COVID patients diagnosed with PE in 62 Spanish EDs (20% of Spanish EDs, case group) during the first COVID outbreak. They formed control groups of COVID patients without PE and non-COVID patients with PE. Adjusted comparisons for baseline characteristics, acute episode characteristics, and outcomes were made between cases and randomly selected controls (1:1 ratio). The authors identified 368 PEs among 74 814 patients with COVID-19 (4.92‰). The standardized incidence of PE in the COVID population was 310 per 100 000 person-years, significantly higher than that observed in the non-COVID population which was 35 per 100 000 person-years, resulting in an odds ratio (OR) of 8.95. Several characteristics in COVID patients were independently associated with PE, the strongest being D-dimer >1000 ng/mL, chest pain, and chronic heart failure (inverse association). COVID patients with PE differed from non-COVID patients with PE in 16 characteristics, most directly related to COVID infection itself; remarkably, D-dimer >1000 ng/mL, leg swelling/pain, and PE risk factors were significantly less present. PE in COVID patients affected smaller pulmonary arteries than in non-COVID patients, while right ventricular dysfunction (RVD) was similar in both groups. In-hospital mortality in COVID patients with PE (16.0%) was like that of COVID patients without PE (16.6%, OR 0.96), but higher than that of non-COVID patients with PE (6.5%, OR 2.74). Adjustment for differences in baseline and acute episode characteristics and sensitivity analysis reported very similar associations (Figure 1). Figure 1 Open in new tabDownload slide Summary of the results of the study that investigated incidence, risk factors, clinical characteristics, and in-hospital mortality in COVID-19 patients with pulmonary embolism (PE) compared with COVID-19 patients without PE and non-COVID-19 patients with PE (from MiróO, Jimenez S, Mebazaa A, Freund Y, Burillo-Putze G, Martín A, Martín-Sánchez FJ, Lamberechts J, Alquézar-ArbeéA, Jacob J, Llorens P, Piñera P, Gil V, Guardiola J, Cardozo C, Módol Deltell JM, Tost J, Aguirre Tejedo A, Palau-Vendrell A, LLauger García L, Adroher Muñoz M, del Arco Galán C, Agudo Villa T, López-Laguna N, López Díez MP, Beddar Chaib F, Quero Motto E, González Tejera M, Ponce MC, González del Castillo J; Spanish Investigators on Emergency Situations TeAm (SIESTA) network. Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome. See pages 3127–3142). Figure 1 Open in new tabDownload slide Summary of the results of the study that investigated incidence, risk factors, clinical characteristics, and in-hospital mortality in COVID-19 patients with pulmonary embolism (PE) compared with COVID-19 patients without PE and non-COVID-19 patients with PE (from MiróO, Jimenez S, Mebazaa A, Freund Y, Burillo-Putze G, Martín A, Martín-Sánchez FJ, Lamberechts J, Alquézar-ArbeéA, Jacob J, Llorens P, Piñera P, Gil V, Guardiola J, Cardozo C, Módol Deltell JM, Tost J, Aguirre Tejedo A, Palau-Vendrell A, LLauger García L, Adroher Muñoz M, del Arco Galán C, Agudo Villa T, López-Laguna N, López Díez MP, Beddar Chaib F, Quero Motto E, González Tejera M, Ponce MC, González del Castillo J; Spanish Investigators on Emergency Situations TeAm (SIESTA) network. Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome. See pages 3127–3142). The authors conclude that PE in COVID patients at ED presentation is unusual (∼0.5%), but the incidence is ∼9-fold higher than in the general (non-COVID) population. Moreover, risk factors and leg symptoms are less frequent, the increase in D-dimer is lower, and emboli involve smaller pulmonary arteries. While PE probably does not increase the mortality of COVID patients, the mortality is higher in COVID than in non-COVID patients with PE. The manuscript is accompanied by an Editorial by John Eikelboom and Noel Chan from the Canada and Hamilton General Hospital and McMaster University in Ontario, Canada.7 The Editorialists conclude that the data provided by Miró and colleagues lend further support to the importance of COVID-19 as a risk factor for venous thrombo-embolism (VTE). At the same time, in the absence of high-quality evidence demonstrating a benefit of therapies that prevent VTE, their finding of a lack of association between PE and death in patients with COVID-19 should prompt further caution in the routine adoption of intensified anticoagulant strategies that can increase bleeding. By reducing blood flow to the lungs, large vessel thrombo-embolism has the potential to worsen respiratory function in patients with COVID-19. However microvascular complications may be the most important thrombo-embolic complications in these patients, and it is unclear if these can be prevented with therapeutic anticoagulation. Consistent with this conclusion, randomized trials of intensified thromboprophylaxis using intermediate or therapeutic doses of anticoagulation have so far failed to demonstrate mortality benefits in a combined total of 4470 hospitalized patients with COVID-19, despite apparently reducing major thrombosis including VTE in some trials. More than 70 randomized trials of antithrombotic therapy are currently ongoing in patients with COVID-19, and their successful completion should help to clarify this issue. International guidelines suggest home treatment in patients with low-risk acute pulmonary PE, when home circumstances are adequate.8 However, current evidence is mainly based on cohort studies using different sets of eligibility criteria. Therefore, controversy persists about the optimal triaging strategy and eligibility criteria for home treatment. In a Clinical Research contribution entitled ‘Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial’, Pierre-Marie Roy from the CHU Angers: Centre Hospitalier Universitaire d’Angers in France, and colleagues compared the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI criteria) in triaging patients with acute PE for home treatment.9 Normotensive patients with PE from 26 hospitals in France, Belgium, the Netherlands, and Switzerland were randomized to triaging either with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician in charge, taking into consideration the patient’s opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent VTE, major bleeding, or all-cause death (non-inferiority analysis with a 2.5% absolute risk difference as the margin) and the rate of patients discharged home within 24 h after randomization. In the intention-to-treat analysis, 38% of the Hestia patients were treated at home vs. 37% of the sPESI patients, with a 30-day composite outcome rate of 1.3% and 1.1%, respectively. No recurrent or fatal PE occurred in either home treatment arm. The authors conclude that for triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI have similar safety and effectiveness. With either tool complemented by the over-ruling of the physician in charge, more than a third of patients can be treated at home with a low incidence of complications. The manuscript is accompanied by an Editorial by Cecilia Becattini from the University of Perugia in Italy and colleagues.10 The authors highlight that HOME-PE is the largest randomized study assessing home management in patients with acute PE and its results can contribute to the progressive refinement in risk stratification and definition of management pathways for patients with acute PE. Home treatment seems feasible in ∼30% of the normotensive patients with acute PE, if adequate patient care is available as an outpatient service. Hestia and sPESI are both able to identify a subgroup of patients with acute PE at low risk for complications, but clinical judgement cannot be completely replaced. Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of acute coronary syndrome (ACS), particularly in women. Its real incidence is probably even higher than reported: indeed, it has been underdiagnosed for years due to the lack of modern diagnostic tools (e.g. intravascular imaging) and low awareness of the disease. Observations collected from contemporary SCAD case series have led to the general consensus that conservative therapy should be considered as first-line approach in the absence of clinical high-risk features: dissections can resolve spontaneously over time after conservative management due to recollection of the intimal flap or resorption of the intramural haematoma.11–13 The role of antiplatelet therapy in patients with SCAD undergoing initial conservative management is still a matter of debate, with theoretical arguments in favour of and against its use. In a Clinical Research article entitled ‘Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection’, Cerrato et al. investigated the 1-year outcome of patients with SCAD managed with initial conservative treatment included in the DIssezioni Spontanee COronariche (DISCO) multicentre international registry.14 Patients were allocated to two groups according to single antiplatelet treatment (SAPT) or double antiplatelet treatment (DAPT) prescription. The primary endpoint was the 12 months incidence of major cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any unplanned percutaneous coronary intervention (PCI). Out of 314 patients included in the DISCO registry, the authors investigated 199 patients in whom SCAD was managed conservatively. Most patients were female (89%), presented with acute coronary syndrome (ACS; 92%), and mean age was 52.3 years. Sixty-seven (33.7%) were given SAPT whereas 132 (66.3%) received DAPT. Aspirin plus either clopidogrel or ticagrelor were prescribed in 63% and 37% of DAPT patients, respectively. Overall, a 14.6% MACE rate was observed at the 12-month follow-up. Patients treated with DAPT had a significantly higher MACE rate than those with SAPT (18.9% vs. 6.0%, HR 2.62; P = 0.013), driven by an early excess of non-fatal MI or unplanned PCI. At multiple regression analysis, type 2a SCAD (OR 3.69; P = 0.007) and DAPT regimen (OR 4.54; P = 0.016) were independently associated with a higher risk of MACE at 12 months (Figure 2). Figure 2 Open in new tabDownload slide Graphical Abstract (from Cerrato E, Giacobbe F, Quadri G, Macaya F, Bianco M, Mori R, Biolé CA, Boi A, Bettari L, Rolfo C, Ferrari F, Annibali G, Scappaticci M, Pavani M, Barbero U, Buccheri D, Cavallino C, Lombardi P, Bernelli C, D’Ascenzo F, Infantino V, Gambino A, Cinconze S, Rognoni A, Montagna L, Porto I, Musumeci G, Escaned J, Varbella F; DISCO Collaborators. Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection. See pages 3161–3171). Figure 2 Open in new tabDownload slide Graphical Abstract (from Cerrato E, Giacobbe F, Quadri G, Macaya F, Bianco M, Mori R, Biolé CA, Boi A, Bettari L, Rolfo C, Ferrari F, Annibali G, Scappaticci M, Pavani M, Barbero U, Buccheri D, Cavallino C, Lombardi P, Bernelli C, D’Ascenzo F, Infantino V, Gambino A, Cinconze S, Rognoni A, Montagna L, Porto I, Musumeci G, Escaned J, Varbella F; DISCO Collaborators. Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection. See pages 3161–3171). Cerrato and colleagues conclude that in this European registry most patients with SCAD undergoing initial conservative management received DAPT. Yet, at 1-year follow-up, DAPT, as compared with SAPT, was independently associated with a higher rate of adverse cardiovascular events. This manuscript is accompanied by an Editorial by Sharonne Hayes from the Mayo Clinic in Rochester, MN, USA.15 Hayes concludes that although the relative rarity of SCAD makes development and completion of randomized prospective trials more challenging, the authors’ ‘counterintuitive’ findings should spur us all on to collaborate and be creative in developing an evidence base upon which to inform our approach to early and long-term management of SCAD. Critically we must continue to gather the evidence necessary so that we ‘first, do no harm’. Bleeding risk associated with the potent antithrombotic drugs utilized in ACS is a topic of growing interest.16–18 Emerging evidence has linked cholesterol metabolism with platelet responsiveness. In a Clinical Research article entitled ‘LDL cholesterol levels and in-hospital bleeding in patients on high-intensity antithrombotic therapy: findings from the CCC-ACS Project’, Xin Zhou from the Tianjin Medical University General Hospital in China, and colleagues sought to examine the dose–response relationship between admission LDL cholesterol (LDL-C) and major in-hospital bleeds in ACS patients.19 Among 42 378 ACS patients treated with PCI enrolled in 192 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with a higher risk at lower LDL-C levels. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted OR 1.49; 95% confidence interval 1.21–1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas, for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, with no difference at higher LDL-C levels. The authors conclude that in a nationwide ACS registry, a non-linear association is identified between admission LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. The contribution is accompanied by an Editorial by Diana Adrienne Gorog from the Imperial College London in the UK, and colleagues.20 The authors note that while the magnitude of benefit of LDL-C reduction in patients with ACS undergoing PCI should trump concerns over lipid-lowering strategies (the average in-hospital TIMI major bleeding rates were below 1.5% and 2% in the lowest LDL-C categories); in addition, low LDL-C on admission among ACS patients undergoing PCI may be a marker of increased susceptibility to bleeding during intensive antithrombotic therapy. Thus, every effort should be made to reduce the risk of bleeding, including with the use of gastrointestinal prophylaxis, radial rather than femoral artery access, good blood pressure control, anticoagulant or parenteral antiplatelet dosing adjusted to weight and renal function, and careful choice of antithrombotic drugs. As noted above, patients with acute PE at low risk for short-term death are candidates for home treatment or short hospital stay. In a Meta-analysis article entitled ‘Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis’, Cecilia Becattini from the University of Perugia in Italy, and colleagues aimed at determining whether the assessment for RVD or elevated brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) improves identification of low-risk patients compared with clinical models alone.21 Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (PESI, sPESI, or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7%. RVD at echocardiography, computed tomography, or BNP/NT-proBNP was significantly associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81), death within 3 months (1.6 vs. 0.4%; OR 4.03), and PE-related death (1.1 vs. 0.04%; OR 22.9). The authors conclude that RVD should be considered to improve identification of low-risk PE patients. The manuscript is accompanied by an Editorial by Marc Humbert from the Université Paris-Saclay in France.22 Humbert and colleagues conclude that Becattini and colleagues provide more evidence to solve a frequently encountered clinical dilemma. A patient with acute PE classified as being at low risk for death, but with abnormal cardiac biomarkers or morphological right ventricular findings, should be managed as an intermediate-risk PE patient, as suggested by the most recent update of the ESC guidelines. The prognosis of low-risk patients with no cardiac involvement is excellent, which should allow outpatient management to be considered as frequently as possible, subject to a well-organized care pathway. The Issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Single antiplatelet therapy after TAVI: clarity on existing data’, George Dangas from the Icahn School of Medicine at Mount Sinai in New York, USA and colleagues comment on the recent publication ‘Management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation: a consensus document of the ESC Working Group on Thrombosis and the European Association of Percutaneous Cardiovascular Interventions (EAPCI), in collaboration with the ESC Council on Valvular Heart Disease’ by Jurrien ten Berg from the The Cardiovascular Research Institute Maastricht (CARIM) in Maastricht, the Netherlands, and colleagues.23,24 ten Berg et al. respond in a separate comment.25 The editors hope that this issue of the European Heart Journal will be of interest to its readers. With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article. 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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Mesko, Bertalan

doi: 10.1093/eurheartj/ehab167pmid: 34038504

Introduction The 21st century has seen major changes in the practice of medicine and the delivery of healthcare through a cultural transformation we call digital health.1 This generation of patients comes with a desire for an equal-level partnership between them and their medical professionals; as well as for a change in the roles of the old status quo. The role of the passive patient has been transforming into a proactive role being eager to get involved with their health and disease management. Physicians’ role of being the key holder to the ivory tower of medicine has been transforming into the role of a guide for their patients in the network of information and technologies (Figure 1). Figure 1 Open in new tabDownload slide Depictions of the traditional setting of a doctor–patient meeting (left) and the new setting characterized by an equal-level partnership, access to data that come from patients and medical professionals, and the shared use of advanced technologies (right). Figure 1 Open in new tabDownload slide Depictions of the traditional setting of a doctor–patient meeting (left) and the new setting characterized by an equal-level partnership, access to data that come from patients and medical professionals, and the shared use of advanced technologies (right). In all this, cardiology has been a prominent example about how the use of advanced technologies, digital health, and automation could shape the future of a medical specialty. Several reasons underscore this notion. 1. The leading cause of death worldwide is ischaemic heart disease, responsible for 16% of deaths, according to the WHO. Since 2000, this disease has seen the largest increase in the number of deaths rising by >2–8.9 million deaths in 2019. 2. Many of the most popular digital health devices on the market measure vital signs and health parameters related to circulation. 3. Most conditions cardiologists deal with require the active engagement of patients on the long term. The COVID-19 pandemic has emphasized these reasons even more. The pandemic has led to a faster adoption of digital health technologies; made telemedicine the main way of providing care in many areas; and accelerated the process of shifting the point-of-care from hospital buildings and practices to wherever patients are.2 This way, by envisioning how these factors shape the future of this medical specialty, cardiology could also pave the way for medical professionals in other fields by helping them better understand what awaits them. The rise of digital health devices A swarm of technologies have become available globally in less than a decade (Figure 2). Digital blood pressure monitors, hand-held electocardiogram (ECG) devices, heart rate and motion trackers, and smartwatches have become accessible to the masses. Combined, portable diagnostic devices have been developed that can measure multiple vital signs and health parameters at once with built-in algorithms that can also immediately analyse the results. Figure 2 Open in new tabDownload slide Examples of digital health devices and sensors focusing on vital signs and health parameters related to circulation. The coloured dots next to each device represent on which body part those have to be used. Figure 2 Open in new tabDownload slide Examples of digital health devices and sensors focusing on vital signs and health parameters related to circulation. The coloured dots next to each device represent on which body part those have to be used. Open in new tabDownload slide Open in new tabDownload slide Millions of patients have started taking direct-to-consumer genetic tests to learn about their risks for major heart conditions; medication sensitivity for a range of drugs used in those conditions and even doing microbiome tests to optimize their diet. This trend has also reached cardiologists in their daily profession through digital stethoscopes, portable ultrasound devices, algorithms analysing medical images, and in the design of treatment pathways. At least five artificial intelligence (AI)-based technologies have been approved by the Food and Drug Administration (FDA) for use in cardiology.3 Examples include Arterys for analysing cardiovascular images from magnetic resonance; ECG analysis support and Eko’s cardiac monitor. Dozens of other technologies have received CE approval for their use in cardiology. It seems clear that automation in analysing patients’ data and decision support will have a growing role in the job of cardiologists. There is an influx of data coming from patients that add to the vast amount of information they already deal with at the point-of-care. At the same time, the access to information and technologies allows patients dealing with cardiovascular issues to get more involved in their care. Both trends in themselves would lead to significant changes in how cardiologists do their job, but, together, the transformation of the medical practice in general is inevitable. A vision about the future of cardiology In 2032, 44-year-old Linda living in the London suburbs decides that she wants to change her lifestyle by running half an hour a few times a week. As she has no experience in doing regular exercises, she chooses a fitness wearable measuring vital signs and other health data to accompany her on the journey. After a few sessions, the device starts sending alerts about detecting an abnormal heart rate and irregularities in her ECG. She uses a chatbot on her phone based on AI to advise her what to do with it. The chatbot suggests sharing the data and the notifications with her primary care physicians who advises her to see a cardiologist. The cardiologist uses an algorithm trained in machine learning to provide a prediction score for how Linda’s case might evolve. The algorithm has access to the data of millions of patients and every decision it makes is confirmed by a physician to further improve its efficiency. Linda received a more advanced device that is continuously connected to her cardiologist’s dashboard to make sure she is being monitored properly and to help decide on preventive treatment. Since the emerging symptoms were already noticed long before anything major could happen, Linda keeps on running without the fear that she might have a heart condition. The final decision always belongs to the cardiologist who suddenly has two new members in the medical team: the patient and AI. While this promise could raise fear or doubt for some about how this might work out, hopefully, the rest will only see what matters: a patient avoiding a heart incident, a physician enjoying their profession, and a healthcare system becoming more efficient through a new equal-level partnership. This is the promise of digital health. With its unique position in the palette of medical specialties, cardiology could be a leading example paving the road for others in how to adopt advanced technologies while focusing on the real-life relationships they can build with patients through compassionate care. Conflict of interest: none declared. References 1 Meskó B , Drobni Z, Bényei É, Gergely B, Győrffy Z. Digital health is a cultural transformation of traditional healthcare . mHealth 2017 ; 3 : 38 – 38 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Sust PP , Solans O, Fajardo JC, Peralta MM, Rodenas P, Gabaldà J, et al. Turning the crisis into an opportunity: digital health strategies deployed during the COVID-19 outbreak . J Med Internet Res 2020 ; 22 . Google Scholar OpenURL Placeholder Text WorldCat 3 Benjamens S , Dhunnoo P, Meskó B. The state of artificial intelligence-based FDA-approved medical devices and algorithms: an online database . NPJ Digit Med 2020 ; 3 : 1 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Escandon, Rafael; Heidecker, Bettina

doi: 10.1093/eurheartj/ehab102pmid: 33677543

What the COVID-19 pandemic has revealed to clinical researchers The magnitude of the success in vaccine and countermeasure research to address the pandemic of SARS-CoV-2 in 2020 cannot be overstated.1 Within a short period of time, the international community teamed up to address one of the greatest challenges in history, leading to unprecedented achievements such as ‘Project Lightspeed’,2,3 in which a highly efficient vaccine against SARS-CoV-2 was developed within months. In parallel, other investigators and companies developed with great efficiency successful vaccines and therapies against SARS-CoV-2, trying to meet the high demand for protection of our society and for return to ‘normal’ life.4,5 While these great successes received extensive media coverage, other scientists have faced challenges due to delayed institutional approvals of their COVID-19 research projects. Certainly, the role of the ethics committee in ensuring the balance between scientific progress and the protection of patients’ rights, privacy, and clinical care is of utmost importance. While the review of a research project application by an ethics committee frequently takes several months during ‘normal times’, this delay may lead to avoidable loss of valuable samples and data during an outbreak of a pandemic. Time is of the essence for the research community during a pandemic as scientists race to elucidate the pathophysiology of the disease and provide guidance to those designing potentially lifesaving public policies. A new pragmatic balance between regulation and productivity in science must be found in such scenarios. In this article, we suggest a two-step consent algorithm, in which we separate the institutional approval process for sample acquisition from the approval process of sample analysis, allowing sample collection to start immediately during an outbreak of a public health emergency. Lost samples during the first peak of the COVID-19 pandemic Our motivation for writing this article arose from anecdotal evidence of missed opportunities during the first peak of the COVID-19 pandemic observed by our international colleagues and by ourselves. In this small-scale collection of data, we found that, on average, 70% of COVID-19 minimal-risk biosamples such as blood or plasma could not be collected during the first wave of the pandemic and were therefore lost due to delays in approvals across many institutions. These delays were caused by an overwhelming number of applications to the ethics committees by investigators aiming to study COVID-19.6 The lost samples could have potentially provided insights into the pathophysiologic mechanisms of COVID-19 in spring 2020 to better prepare the public and clinical facilities for the second peak in autumn 2020. The increased volume of applications required institutions to adjust their review and approval practices.6 While ethical decisions on investigational trials are complex and require a comprehensive and often lengthy review, we suggest a simple and time-efficient approach during a public health crisis for studies that are solely analytical. Early analytical and observational studies are highly relevant as they seek to generate a better understanding of the pathophysiology of a novel disease such as COVID-19 and to improve diagnosis and risk assessment.6 In that regard, relevant discoveries had been made in analytical studies concerning the nature of COVID-19, active viral replication of SARS-CoV-2 in the respiratory tract, and how this affects infectivity of patients during the course of the illness.7 Those findings had a relevant impact on public health procedures. Given the importance of analytical studies, the low health risk they pose to patients, and the observed delays in their approval process, we suggest a two-step consent process that separates sample collection and sample processing, enabling sample collection immediately from the start of the outbreak. Proposal for two-step consent process and exploratory sample collection We suggest a rapid, simple, independent ethics committee (IEC) approved, two-step process to consent for collection of biosamples that involve minimal risk to the donor. Step 1 obtains a consent limited to collection, proper storage, description of the level of personal identifiability, and process for withdrawing consent for donated routine bio-samples such as (blood, plasma, sputum, and urine) until the public health emergency eases. This consent must be approved a priori by the local ethics committee for general health emergencies and may be applied anytime an outbreak such as the current pandemic occurs without requiring an additional approval process. This allows storage of samples right from the start of an outbreak and commits the investigator to proper stewardship of the biosamples. Step 2 of consent is approved as part of the application for a specific analytical analysis, which is submitted to the IECs at a time when the system is less acutely burdened. After approval by the IECs, the Step 2 consent is collected retrospectively from patients whose samples have already been stored and includes more specific details of research objectives and the analyses to be done on their samples. Step 2 consent may be a broad consent, but it must contain adequate details on present and future analyses, storage, data sharing, and rights to discontinue use.8,9 If a patient died between Steps 1 and 2, the Step 2 consent is sought from the nearest family member. If the analyses involve genetic testing, local regulations have to be taken into consideration. If proper consent at Step 2 cannot be obtained, samples are destroyed (Figure 1). Figure 1 Open in new tabDownload slide Proposed 2-step consent process for collection of bio-samples in public health emergencies. Figure 1 Open in new tabDownload slide Proposed 2-step consent process for collection of bio-samples in public health emergencies. With the algorithm of a two-step consent, we would like to offer guidance to institutions who may have experienced similar barriers during the outbreak of the pandemic, when rapid data and sample collection was most needed to obtain insights into this novel disease. Clinical Scientists/Investigators have a(n ethical) responsibility to pursue research which may urgently reduce morbidity and mortality, as well as to be diligent stewards of their ongoing research projects involving human subjects, even during public health emergencies. Any process which slows, halts or handicaps valid and ethical scientific research, affects research utility and integrity. Likewise, academic, public, and private institutions have a similar responsibility to create a policy and offer guidance to investigators on the benefits and risks of approving new, continuing, suspending, or terminating existing research projects during public health emergencies. With our suggested algorithm, we hope that in the future similar clinical scenarios can be addressed more promptly so that the entire scientific community will be able to address these challenges from Day 1 of the outbreak. Conflict of interest: B.H. has received speaker’s fees from Pfizer. Open in new tabDownload slide Open in new tabDownload slide References 1 Ball P . The lightning-fast quest for COVID-19 vaccines and what that means for other disease . Nature 2021 ; 589 : 16 – 18 . 2 Sahin U , Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, Baum A, Pascal K, Quandt J, Maurus D, Brachtendorf S, Lörks V, Sikorski J, Hilker R, Becker D, Eller A-K, Grützner J, Boesler C, Rosenbaum C, Kühnle M-C, Luxemburger U, Kemmer-Brück A, Langer D, Bexon M, Bolte S, Karikó K, Palanche T, Fischer B, Schultz A, Shi P-Y, Fontes-Garfias C, Perez JL, Swanson KA, Loschko J, Scully IL, Cutler M, Kalina W, Kyratsous CA, Cooper D, Dormitzer PR, Jansen KU, Türeci Ö. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses . Nature 2020 ; 586 : 594 – 599 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Mulligan MJ , Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Raabe V, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi P-Y, Türeci Ö, Tompkins KR, Walsh EE, Frenck R, Falsey AR, Dormitzer PR, Gruber WC, Şahin U, Jansen KU. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults . 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Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial . Lancet 2020 ; 396 : 467 – 478 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Gulick RM , Sobieszczyk ME, Landry DW, Hollenberg AN. Prioritizing clinical research studies during the COVID-19 pandemic: lessons from New York City . J Clin Investig 2020 ; 130 : 4522 – 4524 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Wölfel R , Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brünink S, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C. Virological assessment of hospitalized patients with COVID-2019 . Nature 2020 ; 581 : 465 – 469 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Grady C , Eckstein L, Berkman B, Brock D, Cook-Deegan R, Fullerton SM, Greely H, Hansson MG, Hull S, Kim S, Lo B, Pentz R, Rodriguez L, Weil C, Wilfond BS, Wendler D. Broad consent for research with biological samples: workshop conclusions . Am J Bioeth 2015 ; 15 : 34 – 42 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Goldenberg AJ , Maschke KJ, Joffe S, Botkin JR, Rothwell E, Murray TH, Anderson R, Deming N, Rosenthal BF, Rivera SM. IRB practices and policies regarding the secondary research use of biospecimens . BMC Med Ethics 2015 ; 16 : 32 . Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Friedman, Paul A

doi: 10.1093/eurheartj/ehab216pmid: 33948649

Open in new tabDownload slide Open in new tabDownload slide Previously, Dr Friedman served as Director of the Cardiac Implantable Device Lab as well as the Medical Director in the Center for Connected Care at Mayo Clinic. He is a trained electrical engineer, with deep experience in innovation, with over 50 patents issued and several companies founded. He was invited to deliver the prestigious 2020 European Society of Cardiology Paul Hugenholtz Lecture on Innovation. He was also honoured as a top Minnesota inventor. He is an active researcher, with over 400 scientific original publications. He is a committed educator, serving as a director for 5 national and international meetings, editor of 7 textbooks, and author of over 75 book chapters. He is a frequent visiting professor and lecturer at educational meetings. Dr Friedman received his BA in Plan II liberal arts and BS in Electrical Engineering from the University of Texas at Austin. He received his medical degree from Stanford University and trained in internal medicine at the University of Washington, Seattle (internship) and Stanford University. He trained in cardiovascular medicine and cardiac electrophysiology at Mayo Clinic, Rochester, MN, USA. Dr Friedman has a deep interest in analysis and processing of physiologic signals, remote monitoring, and use of technology including wearable and implantable devices to detect and treat physiologic abnormalities. He leads a team that has been developing artificial intelligence tools to detect and treat cardiovascular disease. He has and continues to serve as principal investigator in multicentre global trials testing novel implantable devices, and others utilizing remote monitoring of patient physiologic data. He has experience in co-ordinating research activities, data acquisition, and systems processes across large geographical distances and national boundaries. Clinically, his interests include catheter ablation and implantable device therapy. Conflict of interest: Mayo Clinic has licensed AI technology that Dr. Friedman co-invented to Eko, Anumana, and AliveCor, and medical device technology to MediCool and Murani Health. Mayo Clinic and Dr. Friedman may receive financial benefit from the commercialization of these technologies. Dr. Friedman serves as investigator and/or advisory board member for Medtronic, Boston Scientific, and Abbott, with funds directed to Mayo Clinic. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Geske, Jeffrey B

doi: 10.1093/eurheartj/ehab142pmid: 33764446

Open in new tabDownload slide Open in new tabDownload slide Dr Geske completed his medical training at Mayo Clinic (Rochester, MN, USA), including fellowship in Cardiovascular Diseases and advanced fellowship in Multimodality Cardiovascular Imaging. He was the 2014 recipient of the Mayo Brothers Distinguished Fellowship Award. He is board certified in Cardiovascular Diseases and Echocardiography. Dr Geske is an Associate Professor of Medicine and has been a practicing cardiologist at Mayo Clinic since 2015. Dr Geske’s editorial responsibilities include serving as an Editor for American Heart Journal and Social Media Editor for JACC Cardiovascular Imaging. He has a passion for medical education. Dr Geske’s educational awards include being named Educator of the Year by the Mayo Clinic Alix School of Medicine (2019), the Mayo Clinic School of Health Sciences echocardiography program (2019), and the Mayo Clinic Cardiovascular Diseases fellowship (2019). He currently serves as a co-director of the Mayo Clinic Cardiovascular Board Review. Dr Geske leads the Mayo Clinic Alix School of Medicine cardiovascular curriculum. Dr Geske’s clinical focus is structural heart disease with emphasis on imaging and hypertrophic cardiomyopathy. Dr Geske is part of a specialized group of imagers at Mayo Clinic with expertise in structural interventional guidance, intraoperative echocardiography, and pericardiocentesis. He has served as Vice Chair in the Mayo Clinic Division of Cardiovascular Ultrasound and as a member of American College of Cardiology Imaging Section Leadership Council. He leads the Mayo Clinic hypertrophic cardiomyopathy research programme. Dr Geske has greater than 120 peer-reviewed publications. He has given numerous national and international presentations focused on hypertrophic cardiomyopathy and structural imaging. Dr Geske received the Paul and Ruby Tsai and Family grant in 2019 for clinical hypertrophic cardiomyopathy research and serves as Principal Investigator in multiple ongoing studies in hypertrophic cardiomyopathy. Editors, CardioPulse Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Volpe, Massimo; Patrono, Carlo

doi: 10.1093/eurheartj/ehab501pmid: 34324654

Key points Two cross-sectional analyses were performed on the US population observed over 10 cycles by the National Health and Nutrition Examination Survey (NHANES) (from 1999 through 2018). The aims of these studies were to assess trends in glycaemic, lipid, and blood pressure (BP) control in diabetic patients1 and to estimate the age-standardized prevalence of diabetes and control of cardiovascular (CV) risk factors in the overall population,2 respectively. In the population of 6653 diabetic patients, trends for glycaemic, BP, and lipid control were non-linear. Glycaemic control (glycated haemoglobin level <7.0%) was achieved in a higher percentage of patients in the 2007–10 period [57%; 95% confidence interval (CI), 53–62) compared with 1999–2002 (44%; 95% CI, 39–49), but then declined to 50% (95% CI, 46–55) in 2015–18. The percentage of participants who obtained BP control (mean BP <140/90 mmHg) rose from 64% (95% CI, 59–68) in 1999–2002 to 74% (95% CI, 71–77) in 2011–2014 but then declined to 70% (95% CI, 67–74) in 2015–18, with consistent trends when a more stringent BP target of <130/80 mmHg was considered. The percentage of participants in whom lipid control [non-high-density lipoprotein (HDL) cholesterol level <130 mg/dL, and low-density lipoprotein (LDL) cholesterol level <100 mg/dL in sensitivity analyses] was achieved, increased from 25% (95% CI, 21–30) in 1999–2002 to 52% (95% CI, 49–55) in 2007–10 and subsequently levelled off (56% in 2015–18; 95% CI, 51–60).1 Glycaemic, BP, and lipid control in the diabetic population were obtained in 9% (95% CI, 7–12) of participants in 1999–2002, rising up to 25% (95% CI, 21–29) in 2007–10, but then remaining stable at 22% in 2015–18 (95% CI, 18–27).1 In the second analysis performed in the overall population including 28 143 participants, the estimated age-standardized prevalence of diabetes increased significantly from 10% (95% CI, 9–11) in 1999–2000 to 14% (95% CI, 13–16) in 2017–18 (P for trend <0.001). In 2015–18, 67% (95% CI, 63–70), 48% (95% CI, 45–52), and 60% (95% CI, 54–65) of adults with diabetes achieved HbA1c, BP (<130/80 mmHg) and LDL cholesterol (<100 mg/dL) targets, respectively. The achievement of the goals for all three risk factors was obtained in only 21% of the population (95% CI, 15–27), being even lower in young adults aged 18–44 years (7%) and in non-Hispanic black adults (12%).2 Comment on ‘Trends in Diabetes Treatment and Control in U.S. Adults, 1999–2018’ which was published in the N Engl J Med, doi:10.1056/NEJMsa2032271, and on ‘Trends in Prevalence of Diabetes and Control of Risk Factors in Diabetes Among US Adults, 1999–2018’ which was published in the JAMA, doi:10.1001/jama.2021.9883 Comment These cross-sectional studies1,2 show negative trends in the rate of successful control of diabetes and CV risk factors in the most recent cycle of NHANES. The growing prevalence of diabetes as well as the decline in the achievement of the recommended glycaemic, lipid, and BP therapeutic goals in diabetic patients represent a source of concern, especially in consideration of the heavy CV burden related to diabetes. Although age, racial, and ethnic characteristics of participants remained stable, while education grade, income, and health insurance improved, the prevalence of diabetes significantly increased from 1999–2000 to 2017–18, and adequate glycaemic control was obtained in only 50%1 and 67%2 in the diabetic population in the two analyses. In the diabetic population, BP control declined and lipid control levelled off,1,2 in spite of more stringent recommended targets.3–6 The unsatisfactory results observed in the US population are paralleled in Europe by the reports of the EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) V survey, performed to identify risk factors in high-risk patients with and without diabetes.7 Among the 8261 subjects at very-high CV risk involved in the EUROASPIRE V, only 42% achieved BP level <140/90 mmHg, 54% had glycated haemoglobin level <7.0% and about 70% had LDL cholesterol <70 mg/dL.7 This finding is indeed surprising in consideration of the numerous public campaigns, increased awareness, and much larger availability of effective and safe treatment strategies.3 A possible explanation may be represented by unhealthy lifestyle behaviours together with inadequate drug therapy due to inappropriately low doses of antihypertensive, lipid-lowering, and anti-diabetic medications and underuse of combination therapies. In the NHANES registry, a stabilization in the use of BP-lowering drugs was registered after a 16% increase from 1999–2002 to 2007–10. Statin use increased by 28% from 1999–2002 to 2011–14 before levelling off.1 The percentage of patients who received combination glucose-lowering and antihypertensive therapies declined after 2010, also among subjects with uncontrolled risk factors. Indeed, only 61% of participants with a glycated haemoglobin level ≥7% and 53% of those with a BP ≥140/90 mmHg were treated with more than one medication. This clinical inertia is in contrast with the recommendations of the most recent guidelines, which suggest starting and maintaining treatment with more aggressive therapeutic approaches.3–6 In high-risk diabetic patients, an intensified multifactorial intervention with tight glucose control and use of appropriate doses of renin-angiotensin system blockers, aspirin, and lipid-lowering agents has shown sustained beneficial effects with respect to vascular complications and rates of death from any cause and from CV causes.8 Accordingly, several recent studies and meta-analyses have supported the ‘the lower, the better’ concept in the treatment of hypertension, diabetes, and dyslipidaemia, showing that a tighter control of these risk factors significantly improves CV protection, and prompting progressive reductions in the recommended therapeutic goals.3–6,9,10 Although treatment intensification requires a careful consideration of the risk-benefit ratio, the results of the NHANES surveys1,2 underline the need for more intensive and integrated therapeutic strategies, especially in high-risk patients such as those with diabetes, prompting an urgent ‘call to action’ to promote more effective prevention programmes both at population and individual levels. Public campaigns, education, and physicians should synergistically work to raise awareness of the importance of prevention of diabetes and control of risk factors, as well as to encourage healthy lifestyles, early start of pharmacological treatment, and improvement in the adherence to medical prescriptions. Conflict of interest: M.V. reports personal fees for speaker bureau and/or consulting in Advisory Board from Amgen, Astra Zeneca, Daiichi-Sankyo, Menarini Int, MSD, Novartis Pharma, and Novo Nordisk, outside the submitted work. C.P. reports personal fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, and Zambon, grants from AIFA (Italian Drug Agency) and European Commission, other from Scientific Advisory Board of the International Aspirin Foundation, outside the submitted work. References 1 Fang M , Wang D, Coresh J, Selvin E. Trends in diabetes treatment and control in U.S. adults, 1999-2018 . N Engl J Med 2021 ; 384 : 2219 – 2228 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Wang L , Li X, Wang Z, Bancks MP, Carnethon MR, Greenland P, Feng YQ, Wang H, Zhong VW. Trends in prevalence of diabetes and control of risk factors in diabetes among US adults , 1999 – 2018 . JAMA 2021 ; 25 :e219883. Google Scholar OpenURL Placeholder Text WorldCat 3 Piepoli MF , Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Løchen ML, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group . 2016 European Guidelines on cardiovascular disease prevention in clinical practice: he Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR) . Eur Heart J 2016 ; 37 : 2315 – 2381 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Williams B , Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; ESC Scientific Document Group . 2018 ESC/ESH Guidelines for the management of arterial hypertension . Eur Heart J 2018 ; 39 : 3021 – 3104 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Cosentino F , Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Jüni P, Lettino M, Marx N, Mellbin LG, Östgren CJ, Rocca B, Roffi M, Sattar N, Seferović PM, Sousa-Uva M, Valensi P, Wheeler DC; ESC Scientific Document Group . 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD . Eur Heart J 2020 ; 41 : 255 – 323 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Mach F , Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group . 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk . Eur Heart J 2020 ; 41 : 111 – 188 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Kotseva K , De Backer G, De Bacquer D, Rydén L, Hoes A, Grobbee D, Maggioni A, Marques-Vidal P, Jennings C, Abreu A, Aguiar C, Badariene J, Bruthans J, Castro Conde A, Cifkova R, Crowley J, Davletov K, Deckers J, De Smedt D, De Sutter J, Dilic M, Dolzhenko M, Dzerve V, Erglis A, Fras Z, Gaita D, Gotcheva N, Heuschmann P, Hasan-Ali H, Jankowski P, Lalic N, Lehto S, Lovic D, Mancas S, Mellbin L, Milicic D, Mirrakhimov E, Oganov R, Pogosova N, Reiner Z, Stöerk S, Tokgözoğlu L, Tsioufis C, Vulic D, Wood D; EUROASPIRE Investigators . Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry . Eur J Prev Cardiol 2019 ; 26 : 824 – 835 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Gæde P , Lund-Andersen H, Parving H-H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes . N Engl J Med 2008 ; 358 : 580 – 591 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Ettehad D , Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis . Lancet 2016 ; 387 : 957 – 967 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Blood Pressure Lowering Treatment Trialists' Collaboration . Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis . Lancet 2021 ; 397 : 1625 – 1636 . Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Mehta, Laxmi S; Elkind, Mitchell S V; Achenbach, Stephan; Pinto, Fausto J; Poppas, Athena

doi: 10.1093/eurheartj/ehab346pmid: 34254636

burnout, practice efficiency, professional fulfillment, resiliency, well-being “Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.” —The World Health Organization1 As clinicians, we strive for improved health for our patients; yet, it is increasingly clear that our own well-being is an essential component of the quadruple aim: to improve population health, enhance patient experience, reduce costs, and improve the work life of health care workers.2 Clinician well-being is described as experiencing satisfaction and engagement with work, while also having a feeling of professional fulfillment and a sense of meaning in work.3 Conversely, burnout is an occupational phenomenon that is defined as emotional exhaustion, depersonalization, and a sense of low personal accomplishment in a perceived stressful work environment.4 Although burnout is a sign of clinical distress and a barrier to clinician well-being, its absence alone does not confer a state of well-being. Rather, burnout is one of the more extreme negative components along the spectrum of clinician well-being (Figure 1), and can coexist with other common mental conditions (e.g., anxiety and depression). Figure 1 Open in new tabDownload slide Well-Being in Cardiology. The quadruple aim (left) and the spectrum of burnout symptoms and mental well-being (right). Drivers of burnout and its consequences Over the past several decades, there have been dramatic changes in health care with the evolution of technology, increased regulatory burden, and the exponential growth of clerical burden, partly brought about by the widespread introduction of electronic health records. These developments come at a cost to the well-being and work-life balance of clinicians. There are several key drivers (Figure 2) that can influence clinician burnout when the levels are less than optimal: workload and job demands, efficiency and resources, control over work, work-life integration (WLI), alignment of individual and organizational values, social support/community at work, and meaning in work.3,5 Furthermore, women are under-represented in cardiology and may have more stressors contributing to burnout due to lack of career promotion, inequalities in resources (financial), and disparities in mentorship while working in environments that lack diversity, equity, inclusion, and belonging.6 Figure 2 Open in new tabDownload slide The Personal and Professional Ramifications and Drivers of Burnout and Potential Strategies to Address Clinician Well-Being. The personal and professional ramifications of burnout (left), drivers of burnout (centre circle) when less than optimal levels, and potential strategies to address clinician well-being (right). Unfortunately, there are serious personal and professional costs associated with clinician burnout (Figure 2). Personal ramifications of burnout include higher rates of alcohol abuse, substance use, dysfunctional relationships, depression, and suicide.7–10 Although mental health conditions can occur along the spectrum of burnout, it is important to recognize that not all burned out clinicians will develop mental health conditions, and not all clinicians with mental health conditions will experience burnout. Professional ramifications of clinician burnout include higher rates of medical errors, lower quality of care, decreased patient satisfaction, increased disruptive behavior, and loss of professionalism accompanied by a decreased level of empathy.3,5,11–14 Health system expenditures related to the burnout of staff are steep when taking into account institutional costs due to decreased productivity and increased clinician turnover.15–18 In the past year, the coronavirus disease 2019 pandemic has caused additional strain on clinicians through increased patient mortality, personal and family safety concerns, fear of the unknown, and increased work demands. Although clinician well-being is now openly discussed in the media, the stigma of seeking mental health counseling among clinicians remains. Assessing burnout and its drivers by conducting surveys is a critical step to understanding the factors that need to be addressed to cultivate an engaged and efficient workforce and to mitigate clinician burnout. Hence, burnout is a metric to measure and monitor, whereas clinician well-being is the goal in cardiology and medicine. With this joint opinion, the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and World Heart Federation call for global action in health care reform, research, and policy development to address clinician well-being. Further, we aim to generate awareness about the impact of burnout and potential solutions to improve clinician well-being in cardiovascular medicine. Cardiology burnout data Survey data among 2,274 U.S. cardiologists and fellows-in-training reported that more than one-quarter reported being burned out and almost 50% were stressed; only 23.7% reported that they were enjoying their work. Women reported burnout more frequently compared with men. Also, midcareer cardiologists more frequently reported burnout compared with fellows-in-training and early- or late-career cardiologists. Neither type of practice setting nor type of cardiovascular subspeciality had an impact on burnout, but burned-out respondents did report more time spent in direct clinical practice. Overall, most were satisfied with their career; however, burned-out respondents were less satisfied with achieving their professional goals or their desired financial compensation, and they were less likely to recommend cardiology as a career. Compared with their peers, burned-out physicians were less likely to report feeling valued or being treated fairly at work. Drivers associated with burnout among cardiologists include lack of control over workload, a hectic work environment, misalignment of values, and insufficient documentation time.19 Data among U.S. physicians from all different specialties demonstrated that 39.8% reported burnout and 42.7% satisfaction with WLI, whereas other data among physician assistants and nurses have shown lower burnout rates (35.8% and 29.7%, respectively) and higher WLI rates (65.3% and 55.5%, respectively).20–22 There is a dearth of survey data specific to cardiovascular professionals; however, the drivers of burnout among cardiologists may likely be extrapolated to the cardiovascular workforce. Health care organizational strategies Health care organizations have predominately focused on the concept of “fixing the employee” with individual-focused programs (self-resiliency and stress management training) as the solution to improving well-being; however, much more effort needs to be tailored to systemic issues that affect the work environment. Intentional refinement of practice environments with highly functioning teams within which clinicians can optimally care for patients enables all team members to find value and purpose in their work and can result in improved outcomes for the health care organization and patients. It is imperative for health care organizations to support the psychosocial health of their employees and be accountable for a holistic approach. One such method is the Stanford WellMD Professional Fulfillment Model, which incorporates culture of wellness, practice efficiency, and personal resiliency domains,23 while also taking into account the intrinsic (e.g., recognition, trust, meaning in work) and extrinsic (e.g., call schedule, compensation, technology) driving factors that can be modified. Organizational infrastructure is necessary to provide the foundational means to maintain work environments within which clinicians may thrive. The burnout and wellness hierarchy model, adapted from Maslow’s hierarchy of needs, provides a prioritized stepwise approach for health care leaders to address clinicians’ professional fulfillment: basic physiological and mental health needs first; safety and security second; respect from administrators, colleagues, and patients third; appreciation and interpersonal connection fourth; and finally, resources and time to treat patients and practice medicine fully.24 For instance, some techniques by which health care organizations could foster a healthy and resilient workforce include ensuring adequate rest and recovery time, supplying appropriate personal protective equipment, reducing systemic inefficiencies and improving team dynamics, compensating fairly and transparently, and facilitating more direct time with patients. In addition, health care organizations need to provide employees with a structure to allow for confidential reporting of mistreatment and also to destigmatize clinicians’ access to mental health resources. Hospital credentialing committees need to refine their inquiries into mental health conditions so that it does not perpetuate a culture of either under-reporting of mental health conditions or undertreatment due to the fear of the loss of hospital privileges among clinicians. Regular assessment of clinician burnout is essential to understand the effectiveness of implemented strategic pilot projects. Similar to the concepts of prevention of cardiovascular disease, secondary prevention is achieved with targeted approaches to prevent recurrent burnout; however, investment in primary and primordial prevention is equally crucial to reduce or potentially avoid burnout all together. Role of medical specialty societies Clinician wellness is a broad entity that requires medical specialty societies to develop a multipronged approach to make meaningful progress. To support their members, medical societies will need to continue to provide recommendations to health care organizations and advocate for meaningful health policy changes. Furthermore, development of cardiology-specific tools that may improve practice efficiency or clinician knowledge base in a timely and convenient fashion is imperative. Medical specialty societies are also key in developing a sense of community for their members. Engaged members of medical specialty societies often cite global social networks as a recurring theme for ongoing involvement in societal committees and attendance at national conferences. However, medical societies will need to continue to expand their initiatives in diversity and inclusion so that all members feel valued and have a sense of belonging. In addition, the medical specialty societies will need to consider innovative ways to deliver educational content and offer networking opportunities, especially in light of resource constraints and increased need for virtual platforms. In March 2020, the ACC’s Board of Trustees commissioned the Task Force on Clinician Well-Being to help focus its strategy to address clinician well-being. Several surveys have been launched to assess the prevalence of and drivers of burnout amongst ACC members. Member sections are integrating well-being themes in their various offerings to members, including toolkits, webinars, and conferences. Recent webinars share cardiologists’ perspectives of mental health conditions as well as inform the viewers regarding signs and symptoms of anxiety and depression, encourage treatment, and provide members the contact information for confidential counseling resources. Additionally, clinician well-being was incorporated into the 2020 ACC/AHA Professionalism and Ethics conference, and the formal recommendations were recently published.25 Also, in Europe, nearly 4,000 medical faculty and researchers from 17 ESC member countries in 2018 completed the ESC-sponsored “Culture and Leadership in Cardiology in Europe” C-Change Faculty Survey. Overall, cardiologists and research professionals have high leadership aspirations and a high degree of personal satisfaction in their work. However, approximately one-quarter of individuals did not view their institutions as providing the best opportunities for meaningful work, and one-third did not feel they were supportive of career advancement. The ESC has been using these findings to guide future strategic initiatives that aim to provide appropriate support for cardiologists in Europe and enable satisfaction within their work environment. The ACC, AHA, ESC, and World Heart Federation acknowledge that clinician well-being is paramount to providing high-quality patient care and are committed to improving the well-being of the cardiovascular workforce. Medical specialty societies will need to continue to identify and promote for the reduction of administrative complexities and practice inefficiencies, which are burdensome and hinder professional fulfillment and patient care. Advocating for appropriate initiatives to improve clinician well-being and mental health resources, while also influencing the elimination of non-essential regulation and document requirements, is key. Furthermore, assisting in combatting the stigma of mental health conditions and the negative ramifications by licensing boards of a history of treated medical health conditions are crucial endeavors for medical specialty societies. Collaboration with other specialties is necessary, including leveraging the expertise of psychiatrists and clinical psychologists. The House of Cardiology will continue to work together and strategize to maintain the well-being of our profession and keep the meaning and joy of caring for patients. Conflict of interest: M.S.V,E. serves as an unpaid Officer of the American Heart Association. A.P. reports financial interest in GE. The other authors report no conflicts of interest. The views expressed in this manuscript are those of the authors and therefore do not necessarily reflect the respective policies of the American Heart Association, Inc., the World Heart Federation, the American College of Cardiology, or the European Society of Cardiology. The views expressed in this article are those of the authors and therefore do not necessarily reflect the respective policies of the World Heart Federation, the American College of Cardiology, the American Heart Association, Inc., or the European Society of Cardiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal‘s style. When citing this article, a citation from any of the journals listed is appropriate. This document will co-publish in Circulation, European Heart Journal, and Global Heart. References 1 Constitution of the World Health Organization . 45th edition Geneva, Switzerland : World Health Organization ; 2006 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 2 Bodenheimer T , Sinsky C. From triple to quadruple aim: care of the patient requires care of the provider . Ann Fam Med 2014 ; 12 : 573 – 576 . 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Washington DC : National Academy of Medicine ; 2019 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 7 Oreskovich MR. Alcohol use does not equal abuse-reply . Arch Surg 2012 ; 147 : 786 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Shanafelt TD , Balch CM, Dyrbye L , et al. Special report: suicidal ideation among American surgeons . Arch Surg 2011 ; 146 : 54 – 62 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Dyrbye LN , Thomas MR, Massie FS, Power DV, Eacker A, Harper W, Durning S, Moutier C, Szydlo DW, Novotny PJ, Sloan JA, Shanafelt TD. Burnout and suicidal ideation among U.S. medical students . Ann Intern Med 2008 ; 149 : 334 – 341 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Oreskovich MR , Kaups KL, Balch CM , et al. Prevalence of alcohol use disorders among American surgeons . Arch Surg 2012 ; 147 : 168 – 174 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Shanafelt TD , Balch CM, Bechamps G, Russell T, Dyrbye L, Satele D, Collicott P, Novotny PJ, Sloan J, Freischlag J. Burnout and medical errors among American surgeons . Ann Surg 2010 ; 251 : 995 – 1000 . Google Scholar Crossref Search ADS PubMed WorldCat 12 West CP , Huschka MM, Novotny PJ, Sloan JA, Kolars JC, Habermann TM, Shanafelt TD. Association of perceived medical errors with resident distress and empathy: a prospective longitudinal study . JAMA 2006 ; 296 : 1071 – 1078 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Williams ES , Manwell LB, Konrad TR, Linzer M. The relationship of organizational culture, stress, satisfaction, and burnout with physician-reported error and suboptimal patient care: results from the MEMO study . Health Care Manage Rev 2007 ; 32 : 203 – 212 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Haas JS , Cook EF, Puopolo AL, Burstin HR, Cleary PD, Brennan TA. Is the professional satisfaction of general internists associated with patient satisfaction? J Gen Intern Med 2000 ; 15 : 122 – 128 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Shanafelt T , Goh J, Sinsky C. The business case for investing in physician well-being . JAMA Intern Med 2017 ; 177 : 1826 – 1832 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Williams ES , Konrad TR, Scheckler WE, Pathman DE, Linzer M, McMurray JE, Gerrity M, Schwartz M. Understanding physicians' intentions to withdraw from practice: the role of job satisfaction, job stress, mental and physical health. 2001 . Health Care Manage Rev 2010 ; 35 : 105 – 115 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Dewa CS , Loong D, Bonato S, Thanh NX, Jacobs P. How does burnout affect physician productivity? A systematic literature review . BMC Health Serv Res 2014 ; 14 : 325 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Shanafelt TD , Raymond M, Kosty M, Satele D, Horn L, Pippen J, Chu Q, Chew H, Clark WB, Hanley AE, Sloan J, Gradishar WJ. Satisfaction with work-life balance and the career and retirement plans of US oncologists . J Clin Oncol 2014 ; 32 : 1127 – 1135 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Mehta LS , Lewis SJ, Duvernoy CS, Rzeszut AK, Walsh MN, Harrington RA, Poppas A, Linzer M, Binkley PF, Douglas PS , American College of Cardiology Women in Cardiology Leadership Council Burnout and career satisfaction among U.S. cardiologists . J Am Coll Cardiol 2019 ; 73 : 3345 – 3348 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Shanafelt TD , West CP, Sinsky C, Trockel M, Tutty M, Satele DV, Carlasare LE, Dyrbye LN. Changes in burnout and satisfaction with work-life integration in physicians and the general US working population between 2011 and 2017 . Mayo Clin Proc 2019 ; 94 : 1681 – 1694 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Dyrbye LN , West CP, Halasy M, O'Laughlin DJ, Satele D, Shanafelt T. Burnout and satisfaction with work-life integration among PAs relative to other workers . JAAPA 2020 ; 33 : 35 – 44 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Dyrbye LN , West CP, Johnson PO, Cipriano PF, Beatty DE, Peterson C, Major-Elechi B, Shanafelt T. Burnout and satisfaction with work–life integration among nurses . J Occup Environ Med 2019 ; 61 : 689 – 698 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Stanford Medicine. The Stanford Model of Professional Fulfillment. Available at:. https://wellmd.stanford.edu/about/model-external.html. 24 Shapiro DE , Duquette C, Abbott LM, Babineau T, Pearl A, Haidet P. Beyond burnout: a physician wellness hierarchy designed to prioritize interventions at the systems level . Am J Med 2019 ; 132 : 556 – 563 . Google Scholar Crossref Search ADS PubMed WorldCat 25 Benjamin IJ , Valentine CM, Oetgen WJ , Sheehan KA, Brindis RG, Roach WH Jr, Harrington RA, Levine GN, Redberg RF, Broccolo BM, Hernandez AF, Douglas PS, Piña IL, Benjamin EJ, Coylewright MJ, Saucedo JF, Ferdinand KC, Hayes SN, Poppas A, Furie KL, Mehta LS, Erwin JP 3rd, Mieres JH, Murphy DJ Jr, Weissman G, West CP, Lawrence WE Jr, Masoudi FA, Jones CP, Matlock DD, Miller JE, Spertus JA, Todman L, Biga C, Chazal RA, Creager MA, Fry ET, Mack MJ, Yancy CW, Anderson RE. 2020 American Heart Association and American College of Cardiology Consensus Conference on Professionalism and Ethics: a consensus conference report . Circulation 2021 ; 143 : e1035 – e1087 . Google Scholar PubMed OpenURL Placeholder Text WorldCat The article has been co-published with permission in the European Heart Journal, the Journal of the American College of Cardiology, Circulation, and Global Heart. © The Author(s) 2021. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. The article has been co-published with permission in the European Heart Journal, the Journal of the American College of Cardiology, Circulation, and Global Heart. © The Author(s) 2021.

Miró, Òscar; Jiménez, Sònia; Mebazaa, Alexandre; Freund, Yonathan; Burillo-Putze, Guillermo; Martín, Alfonso; Martín-Sánchez, Francisco Javier; García-Lamberechts, Eric Jorge; Alquézar-Arbé, Aitor; Jacob, Javier; Llorens, Pere; Piñera, Pascual; Gil, Víctor;

Roy, Pierre-Marie; Penaloza, Andrea; Hugli, Olivier; Klok, Frederikus A; Arnoux, Armelle; Elias, Antoine; Couturaud, Francis; Joly, Luc-Marie; Lopez, Raphaëlle; Faber, Laura M; Daoud-Elias, Marie; Planquette, Benjamin; Bokobza, Jérôme; Viglino, Damien; Schmidt, Jeannot; Juchet, Henry; Mahe, Isabelle; Mulder, Frits; Bartiaux, Magali;

Becattini, Cecilia; Cimini, Ludovica Anna; Agnelli, Giancarlo

doi: 10.1093/eurheartj/ehab491pmid: 34387674

This editorial refers to ‘Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial’, by P.M. Roy et al., doi:10.1093/eurheartj/ehab373. Graphical Abstract Open in new tabDownload slide Graphical Abstract Open in new tabDownload slide Pulmonary embolism (PE) is a potentially life-threatening disease and the third most common cause of cardiovascular death.1 However, risk of death differs substantially across patients with acute PE according to a continuous spectrum of disease severity that results from different combinations of clinical features, right ventricle overload, troponin levels, and other biomarker abnormalities (brain natriuretic peptide and others).2–4 In this complex clinical setting, clinical prediction models based on vital parameters and medical history can accurately identify patients with acute PE at low risk for death.5 The Pulmonary Embolism Severity Index (PESI) and the Geneva score were the first to be proposed and validated for risk stratification of patients with acute PE.5 The simplified version of the PESI score (sPESI) based on the assessment of six items (age, systolic blood pressure, heart rate, oxygen saturation, cancer, chronic obstructive pulmonary disease, or heart failure) allows identification of patients with acute PE and 30-day mortality as low as ∼1% (upper 95% confidence limit 2.1).6 However, this score may appear too strict to fully summarize a medical judgement. In fact, in sPESI, age, blood pressure, and heart rate are assessed by the use of cut-off values, and cancer qualifies for adverse outcome regardless of staging or ongoing anticancer treatment. A more pragmatic approach based on the assessment of 11 criteria—the Hestia criteria—has been proposed to select low-risk patients for outpatient management.7 In a prospective study, 90-day mortality was 1% in patients with acute PE and none of the Hestia criteria for hospitalization who were managed as outpatients (upper 95% confidence limit 2.9).7 Limited evidence exists on the use of sPESI to drive home treatment in patients with acute PE, while Hestia criteria have been derived and validated for this purpose. The sPESI score and the HESTIA criteria have been endorsed by the current guidelines from the European Society of Cardiology for risk assessment and decision-making in patients with acute PE.8 Based on the same bulk of evidence but on a different medical approach, North American guidelines suggest not to replace clinical judgement with the use of clinical scores to predict outcome and make decisions on the management of patients with acute PE.9 Prediction models are increasingly used to complement clinical reasoning and decision-making in a number of clinical conditions and in the cardiovascular domain in particular (e.g. acute chest pain, atrial fibrillation, or transient ischaemic attack). Due to their simple structure, clinical models allow rapid bedside risk stratification and can drive decision-making concerning treatment and patient allocation. Preliminary data suggest similar outcomes in patients with acute PE managed based on clinical gestalt or on PESI/sPESI scores or Hestia criteria.10 However, the best strategy for selection of candidates for home treatment among patients with acute PE is still undefined. In this issue of the European Heart Journal, Roy and colleagues report on a management study on the use of sPESI or Hestia criteria to triage patients with acute symptomatic PE for home treatment.11 In four European countries, 1975 normotensive patients with acute PE were randomized to be designated for home treatment based on either sPESI or the Hestia criteria. A specific patient pathway was set up before study initiation at all study centres to ensure that a dedicated clinical team could provide 24-h care by telephone service for patients discharged home. The primary outcome of the study—the composite of recurrent venous thrombo-embolism, major bleeding, or all-cause death at 30 days—occurred in 3.82% and in 3.57% of the patients randomized to triaging by Hestia or sPESI, respectively. Hestia was non-inferior to sPESI for triaging normotensive patients with acute symptomatic PE. The results of this study should be interpreted taking into account some methodological aspects. Physicians in charge were allowed to overrule the sPESI and Hestia qualification for home treatment; according to the open study design, attending physicians were not blinded concerning the results of patients’ assessment by the comparator strategy (Hestia in patients randomized to sPESI, and vice versa) and concerning other predictors such as right ventricular dysfunction or troponin assessment. These elements of the study design could have reduced the impact of the randomized strategy on the clinical outcome. In this view, HOME-PE should be seen as a comparison of the feasibility of Hestia-driven vs. sPESI-driven management rather than an impact study. Finally, the individual values of the components of the primary composite endpoint—recurrent thrombo-embolism, death, and major bleeding—are probably different in the short-term after acute PE. In HOME-PE, Hestia identified a lower proportion of patients as candidates for home treatment compared with sPESI (39.4% vs. 48.4%), but the proportion of patients actually managed at home was similar in the two triaging groups (38.4% vs. 36.3% in the Hestia and sPESI groups, respectively). The different performance can be explained by the different nature of the two strategies. sPESI is focused on the assessment of predictors of death, while Hestia includes assessment of predictors of death, bleeding, and feasibility of outpatient care (Graphical Abstract). The incidence of recurrent venous thrombo-embolism, major bleeding, or death in patients who qualified for home treatment by the Hestia or sPESI strategy and were actually treated at home was as low as 1.3% and 1.1%, respectively. Death at 30 days occurred in 0.27% and 0.28% of the patients, respectively. Such low incidences may represent acceptable failure rates for clinicians. Rates of the composite outcome and, more importantly, of death were ∼50% lower in patients actually treated at home based on final medical judgement compared with those of patients who qualified for home treatment by the allocated risk stratification strategy. This 50% gap suggests the appropriateness of the final medical judgement over that of the rules. Whether other predictors (right ventricular dysfunction or injury) also influenced final judgement concerning home treatment remains undefined. In fact, in patients with acute PE at low risk according to clinical models, right ventricular dysfunction is associated with early mortality.12 To date, two randomized clinical trials (445 patients) have compared hospitalization with home management in patients with PE deemed at low risk based on PESI or Hestia, one study for each.13 No significant difference was reported in all-cause mortality, recurrent PE, and major bleeding with hospitalization or home treatment, but the overall level of evidence is low. Recently, a large prospective cohort study confirmed the safety of home management in patients with acute PE selected on the basis of the Hestia criteria and on the absence of right ventricular dysfunction.14 However, in everyday clinical practice, only one in every 13 PE patients eligible for home treatment is treated at home and less than half of the low-risk population are hospitalized for 5 days or less.15 HOME-PE suggests that creating physician awareness and structural facilities makes home treatment feasible in ∼35% of normotensive patients with acute PE. This finding mirrors the results obtained in the USA by Vinson and colleagues.16 These authors showed that the implementation and promotion of a clinical decision support system to aid physicians in decision-making for patients with acute PE safely increased outpatient management (17.4% pre- to 28.0% post-intervention). In clinical practice, hospitalization is chosen by clinicians to complete observation for the occurrence of clinical deterioration and education for anticoagulant treatment and by patients because hospitalization seems safe and protective. Indeed, ∼5% of patients treated at home in the HOME-PE study required unscheduled hospitalization during the study period. Whether initial hospitalization would have avoided these events is unknown. However, physicians and patients should be aware of the risk and severity of hospital-acquired complications more than the costs of undue hospitalizations. HOME-PE should be considered in the context of recent challenges in the management of patients with acute PE. The shift in the diagnostic paradigm from the intention of confirming PE in patients with high pre-test probability to that of excluding PE in patients with low pre-test probability led to an increased diagnosis of minor PEs in paucisymptomatic patients.17 The expanding armamentarium of anticoagulant agents moved from continuous infusion of unfractionated heparin with unpredictable effects to the use of low molecular weight heparin, and now to direct oral anticoagulants with predictable dose response, rapid onset of action, and no need for laboratory monitoring.7 These agents have improved the quality of anticoagulation in patients with acute PE. Both of these challenges probably contribute to make home treatment or short hospital stay feasible and safe in selected patients with acute PE. In conclusion, HOME-PE is definitely the largest randomized study assessing home management in patients with acute PE and its results can contribute to the progressive refinement in risk stratification and definition of management pathways for patients with acute PE. Home treatment seems feasible in ∼30% of the normotensive patients with acute PE, if adequate patient care is available as an outpatient service. Hestia and sPESI are both able to identify a subgroup of patients with acute PE at low risk for complications, but clinical judgement cannot be completely replaced. Conflict of interest: C.B. has received personal fees from Bayer HealthCare, Bristol Myers Squibb, and Daiichi Sankyo. D.C. has received lecture fees from Bayer HealthCare, Bristol Myers Squibb, and Daiichi Sankyo. L.A.C. has no conflicts to declare. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. 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