Conduct of Clinical Trials in the Era of COVID-19 Psotka, Mitchell A.; Abraham, William T.; Fiuzat, Mona ...
Journal of the American College of Cardiology,
11/2020, Volume:
76, Issue:
20
Journal Article
Peer reviewed
Open access
The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to ...this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.
•
The COVID-19 pandemic has profoundly affected patient care and the conduct of clinical trials.
•
HF-ARC scientific expert panel developed recommendations for the conduct and analysis of heart failure trials during the pandemic.
•
The HF-ARC consensus recommendations support ongoing clinical trials and strengthen the clinical trial ecosystem, which should have sustained benefits in the future.
Viral respiratory infections are risk factors for cardiovascular disease (CVD). Underlying CVD is also associated with an increased risk of complications following viral respiratory infections, ...including increased morbidity, mortality, and health care utilization. Globally, these phenomena are observed with seasonal influenza and with the current coronavirus disease 2019 (COVID-19) pandemic. Persons with CVD represent an important target population for respiratory virus vaccines, with capacity developed within 3 large ongoing influenza vaccine cardiovascular outcomes trials to determine the potential cardioprotective effects of influenza vaccines. In the context of COVID-19, these international trial networks may be uniquely positioned to redeploy infrastructure to study therapies for primary and secondary prevention of COVID-19. Here, we describe mechanistic links between influenza and COVID-19 infection and the risk of acute cardiovascular events, summarize the data to date on the potential cardioprotective effects of influenza vaccines, and describe the ongoing influenza vaccine cardiovascular outcomes trials, highlighting important lessons learned that are applicable to COVID-19.
•
Viral respiratory infections, such as seasonal influenza and COVID-19, are associated with elevated risks of cardiovascular events.
•
Several international CVOTs are investigating whether seasonal influenza vaccine reduces the risk of cardiovascular events among patients with HF or coronary artery disease.
•
Existing trial networks may provide an opportunity to assess primary and secondary prevention strategies for patients with CVD at risk of complications from COVID-19.
Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to ...claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine.
•
Well-conducted RCTs have repeatedly contradicted practices supported by common sense and clinical observation.
•
Common sense and clinical observation fail because of the inability to fully understand complex biopsychosocial systems.
•
RCTs must be integrated into clinical practice to improve the evidence base in cardiology.
Standard evaluation and management of the patient with suspected or proven cardiovascular complications of coronavirus disease-2019 (COVID-19), the disease caused by severe acute respiratory syndrome ...related-coronavirus-2 (SARS-CoV-2), is challenging. Routine history, physical examination, laboratory testing, electrocardiography, and plain x-ray imaging may often suffice for such patients, but given overlap between COVID-19 and typical cardiovascular diagnoses such as heart failure and acute myocardial infarction, need frequently arises for advanced imaging techniques to assist in differential diagnosis and management. This document provides guidance in several common scenarios among patients with confirmed or suspected COVID-19 infection and possible cardiovascular involvement, including chest discomfort with electrocardiographic changes, acute hemodynamic instability, newly recognized left ventricular dysfunction, as well as imaging during the subacute/chronic phase of COVID-19. For each, the authors consider the role of biomarker testing to guide imaging decision-making, provide differential diagnostic considerations, and offer general suggestions regarding application of various advanced imaging techniques.
•
COVID-19 infections frequently associate with cardiac injury, which increases the risk of morbidity and mortality.
•
Advanced imaging facilitate diagnosis but should be used to inform a change in management.
•
The impact of imaging on patient management during the chronic phase of COVID-19 warrants additional investigation.
Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death. ...These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations. The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients. Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury. The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.
•
Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.
•
Increases can be due to chronic injury, acute nonischemic injury, or acute MI.
•
Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.
Based on Life Design approach, the study aimed at examining the relationship between some constructs relevant for adolescents to handle the current labor market and their role in affecting career ...decidedness: career adaptability, positive attitude toward the future, and future orientation. Specifically, the fully mediational role of positive attitude toward the future and future orientation on the relationship between career adaptability and career decidedness was tested. We involved 774 adolescents, of which 408 boys and 366 girls. Results showed that career adaptability predicted indirectly, through positive attitude toward the future and future orientation, career decidedness. As regards practical implication, the results carried out emphasize the importance to support career adaptability, hope, optimism, and future orientation in adolescence.
•A mediational model between career adaptability and career decidedness is tested.•Positive attitude toward the future and future orientation as mediators are examined.•Career adaptability predicts indirectly decidedness about career choice.
Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the ...venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.
•
COVID-19 may predispose patients to arterial and venous thrombosis.
•
Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19. The optimal preventive strategy warrants further investigation.
•
Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.
•
The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.
Atrial Fibrillation Chung, Mina K.; Refaat, Marwan; Shen, Win-Kuang ...
Journal of the American College of Cardiology,
04/2020, Volume:
75, Issue:
14
Journal Article
Peer reviewed
Atrial fibrillation (AF) is an increasingly prevalent arrhythmia; its pathophysiology and progression are well studied. Stroke and bleeding risk models have been created and validated. Decision tools ...for stroke prophylaxis are evolving, with better options at hand. Utilization of various diagnostic tools offer insight into AF burden and thromboembolic risk. Rate control, rhythm control, and stroke prophylaxis are the cornerstones of AF therapy. Although antiarrhythmic drugs are useful, AF ablation has become a primary therapeutic strategy. Pulmonary vein isolation is the cornerstone of AF ablation, and methods to improve ablation safety and efficacy continue to progress. Ablation of nonpulmonary vein sites is increasingly being recognized as an important strategy for treating nonparoxysmal AF. Several new ablation techniques and technologies and stroke prophylaxis are being explored. This is a contemporary review on the prevalence, pathophysiology, risk prediction, prophylaxis, treatment options, new insights for optimizing treatment outcomes, and emerging concepts of AF.
Display omitted
•AF is a cardiovascular pandemic with a complex pathophysiology and contributes to significant patient morbidity and mortality.•Emphasis is on early detection and intervention for stroke prophylaxis and disease progression.•Significant progress has been made in paroxysmal AF, but better understanding is needed on substrate progression, evolution of non-PV triggers, and a comprehensive approach to multisystem risk factor modification.
Patients with structural heart disease are at increased risk of adverse outcomes from the coronavirus disease-2019 (COVID-19) due to advanced age and comorbidity. In the midst of a global pandemic of ...a novel infectious disease, reality-based considerations comprise an important starting point for formulating clinical management pathways. The aims of these “crisis-driven” recommendations are: 1) to ensure appropriate and timely treatment of structural heart disease patients; 2) to minimize the risk of COVID-19 exposure to patients and health care workers; and 3) to limit resource utilization under conditions of constraint. Although the degree of disruption to usual practice will vary across the United States and elsewhere, we hope that early experiences from a heart team operating in the current global epicenter of COVID-19 may prove useful for others adapting their practice in advance of local surges of COVID-19.
People are using the future to search for better ways to achieve sustainability, inclusiveness, prosperity, well-being and peace. In addition, the way the future is understood and used is changing in ...almost all domains, from social science to daily life. This book presents the results of significant research undertaken by UNESCO with a number of partners to detect and define the theory and practice of anticipation around the world today. It uses the concept of ‘Futures Literacy’ as a tool to define the understanding of anticipatory systems and processes – also known as the Discipline of Anticipation. This innovative title explores: •• new topics such as Futures Literacy and the Discipline of Anticipation; •• the evidence collected from over 30 Futures Literacy Laboratories and presented in 14 full case studies; •• the need and opportunity for significant innovation in human decision-making systems. This book will be of great interest to scholars, researchers, policy-makers and students, as well as activists working on sustainability issues and innovation, future studies and anticipation studies.
PDF
