The definitions for nonvalvular and valvular AF, which can be crucial to selecting appropriate anticoagulation therapy, are blurred and may even be outmoded. Note that some guidelines did not define these terms at all.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"7799",leadTitle:null,fullTitle:"Digital Leadership - A New Leadership Style for the 21st Century",title:"Digital Leadership",subtitle:"A New Leadership Style for the 21st Century",reviewType:"peer-reviewed",abstract:"Digital leadership has been seen as a phenomenon allowing competitive advantages for organizations, but some studies do not include the risks, benefits, and challenges of this type of leadership. Consequently, the objective of this book is to fill this gap by combining several studies from different perspectives. The various chapters presented here follow several approaches and applications that researchers explore in different contexts. This book intends therefore to add to the body of knowledge in leadership and digital areas. On the other hand, this work shows how digital leadership can stimulate organizational development in various countries and regions worldwide.",isbn:"978-1-78985-036-9",printIsbn:"978-1-78985-035-2",pdfIsbn:"978-1-78985-399-5",doi:"10.5772/intechopen.77615",price:119,priceEur:129,priceUsd:155,slug:"digital-leadership-a-new-leadership-style-for-the-21st-century",numberOfPages:170,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"04acd8ff54f1ae641699692e90c508b3",bookSignature:"Mario Franco",publishedDate:"April 1st 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7799.jpg",numberOfDownloads:9467,numberOfWosCitations:2,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:18,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:31,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 7th 2019",dateEndSecondStepPublish:"June 17th 2019",dateEndThirdStepPublish:"August 16th 2019",dateEndFourthStepPublish:"November 4th 2019",dateEndFifthStepPublish:"January 3rd 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"105529",title:"Dr.",name:"Mário",middleName:null,surname:"Franco",slug:"mario-franco",fullName:"Mário Franco",profilePictureURL:"https://mts.intechopen.com/storage/users/105529/images/system/105529.jpg",biography:"Mário Franco is an Associate Professor of Entrepreneurship and SME Administration at the Department of Management and Economics, Beira Interior University, Portugal. He received his Ph.D. in Management from Beira Interior University in 2002. In 1997, he was a doctoral candidate and participated in the European Doctoral Programme in Entrepreneurship and Small Business Management in Spain and Sweden. He is the director of the 2nd Cycle (Master) of Management. His research focuses on strategic alliances, business networks, innovation, and business creation. He is a member of a research unit at the Center for Advanced Studies in Management and Economics of the University of Beira Interior (CEFAGE-UBI) and is currently involved in several research projects on SMEs. He has authored several articles published in journals such as Long Range Planning, R&D Management, International Entrepreneurship and Management Journal, and Management Decision, and some books and book chapters published by international publishers.",institutionString:"University of Beira Interior",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"University of Beira Interior",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"438",title:"Leadership",slug:"leadership"}],chapters:[{id:"69892",title:"Leadership in the Digital Realm: What Are the Main Challenges?",doi:"10.5772/intechopen.89856",slug:"leadership-in-the-digital-realm-what-are-the-main-challenges-",totalDownloads:1035,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The current book chapter examines how digital leaders cultivate opportunities and address risks in a fast-moving, digital market environment. The focal point is to understand if digital leaders are able to keep control over all mechanisms triggered by the turbulent business environment. The chapter’s challenge is to verify how digital leadership works in the specific context of aerospace industry through the case of the Boeing Company.",signatures:"Valentina Della Corte, Giovanna Del Gaudio and Fabiana Sepe",downloadPdfUrl:"/chapter/pdf-download/69892",previewPdfUrl:"/chapter/pdf-preview/69892",authors:[{id:"298561",title:"Prof.",name:"Valentina",surname:"Della Corte",slug:"valentina-della-corte",fullName:"Valentina Della Corte"},{id:"298563",title:"Dr.",name:"Giovanna",surname:"Del Gaudio",slug:"giovanna-del-gaudio",fullName:"Giovanna Del Gaudio"},{id:"299415",title:"Dr.",name:"Fabiana",surname:"Sepe",slug:"fabiana-sepe",fullName:"Fabiana Sepe"}],corrections:null},{id:"70317",title:"Leadership for Digital Working: Towards a Contextual Ambidextrous Approach",doi:"10.5772/intechopen.90370",slug:"leadership-for-digital-working-towards-a-contextual-ambidextrous-approach",totalDownloads:870,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter focuses on Smart Working (SW) adoption and its related leadership styles. We particularly aim at understanding how SW adoption requires an ambidextrous approach based both on directive and empowering leadership. Our theoretical framework, particularly, contextualizes the leadership approach by highlighting that within such blended context (off-site and on-site working mode), leadership should be ambidextrous, according to the specific working mode and, therefore, according to the opposite related dynamics, such as autonomy vs. control or task vs. objectives focus. The model, moreover, focuses on the importance of enabling an approach that implies new relational skills (or new combination of such skills) both for the leaders and the workers that, regarding their remote or physically approach, should evaluate to be more or less directive (or empowering). However, other contingencies should be analysed in order to have a deeper view for a successful SW adoption. Leaders and followers, therefore, need to be cognizant and aware about such contingent approach that claims for their flexibility and variety of behaviors, and they should develop, accordingly, a related behavioral repertoire. This contribution, by proposing a more complete and complex approach for SW adoption based on ambidextrous leadership, offers an original point of view that highlights the importance of balancing both directive and empowering leadership styles within a SW context.",signatures:"Daniele Binci and Francesco Scafarto",downloadPdfUrl:"/chapter/pdf-download/70317",previewPdfUrl:"/chapter/pdf-preview/70317",authors:[{id:"308174",title:"Ph.D.",name:"Daniele",surname:"Binci",slug:"daniele-binci",fullName:"Daniele Binci"},{id:"308545",title:"Prof.",name:"Francesco",surname:"Scafarto",slug:"francesco-scafarto",fullName:"Francesco Scafarto"}],corrections:null},{id:"70252",title:"Competitive Advantage Leadership in the Ultra Modern Era",doi:"10.5772/intechopen.90080",slug:"competitive-advantage-leadership-in-the-ultra-modern-era",totalDownloads:904,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The environment in the ultra modern era is changing rapidly and the business competition is very sharp, so there is a need for a new leadership style. Company leaders’ need have good managerial and entrepreneurial skills, namely proactively managing change to benefit from opportunities arised. The leader is to have the best quality of leadership to lead and continue to adapt to the dynamics of environmental and market developments. They are supported by prime human capital to take advantage of their organizations. An ultra modern era leadership style with managerial abilities that proactively manages the changes and takes advantage of opportunities is mean managerial leadership. Entrepreneurial leadership is a person who has the quality to lead and constantly adapt to the changing environment and market to take advantage of his organization, and the concept of entrepreneurial leadership synergizes with managerial leadership that has been applied and developed in various business institutions and nonprofit organizations. Key factors in implementing human capital are people and skills, creating value for the organization—people as assets, remuneration, training, development and empowerment, and career development to promote the success of the performance of an organization or company.",signatures:"Tjiptogoro Dinarjo Soehari and Iffah Budiningsih",downloadPdfUrl:"/chapter/pdf-download/70252",previewPdfUrl:"/chapter/pdf-preview/70252",authors:[{id:"309766",title:"Dr.",name:"Tjiptogoro",surname:"Soehari",slug:"tjiptogoro-soehari",fullName:"Tjiptogoro Soehari"},{id:"309981",title:"Dr.",name:"Iffah",surname:"Budiningsih",slug:"iffah-budiningsih",fullName:"Iffah Budiningsih"}],corrections:null},{id:"69669",title:"Digital Leader-Followership for the Digital Age: A North American Perspective",doi:"10.5772/intechopen.89820",slug:"digital-leader-followership-for-the-digital-age-a-north-american-perspective",totalDownloads:970,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"This chapter examines the emerging literature on contemporary leadership, particularly leadership in the digital age, digital leadership, e-leadership, and cyber leadership, in the context of socio-cultural changes, theoretical shifts in leadership studies, and leadership education changes observed in the United States in the last two decades. Although the above literature shows a shift from leader-centered and hierarchical to follower-centered and relational leadership, it is not clear how the old may yield to the new paradigm of leadership. There seem to be no discussion in the leadership literature on how to transition from pre-digital to digital era of leadership. While this study acknowledges the discontinuity and tension between the contemporary and the traditional leadership approaches, it offers theoretical and practical alternatives for transitioning from traditional to contemporary leadership in the digital age. Since leadership research has already shifted from single-role identity to multiple-role identities, which enables individuals to acquire and master both leading and following skills in today’s organizations, this study is optimistic that the leader-follower trade (LFT) or similar approaches may build bridges between digital native and digital immigrant generations of leader-followers for a smoother transition from hierarchical to distributed, shared, collective, and adaptive leadership for the digital age.",signatures:"Petros G. Malakyan",downloadPdfUrl:"/chapter/pdf-download/69669",previewPdfUrl:"/chapter/pdf-preview/69669",authors:[{id:"308316",title:"Ph.D.",name:"Petros",surname:"Malakyan",slug:"petros-malakyan",fullName:"Petros Malakyan"}],corrections:null},{id:"68710",title:"Complex Adaptive Team Systems (CATS): Scaling of a Team Leadership Development Model",doi:"10.5772/intechopen.88743",slug:"complex-adaptive-team-systems-cats-scaling-of-a-team-leadership-development-model",totalDownloads:920,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Complex adaptive systems (CAS) have been identified as being hard to comprehend, composed of multiple interacting components acting interdependently with overlapping functions aimed at adapting to external/environmental forces. The current theoretical model utilized the natural functions of teams, viewing teams as a complex adaptive system, to develop the structure of the theory of complex adaptive team systems (CATS). The CATS model was formulated around the components of complexity theory (interactions, nonlinearity, interdependency, heterogeneity, complex systems, emergence, self-organizing, and adaptability) to show its utility across multiple domains (the role of leadership, organizational learning, organizational change, collective cognitive structures, innovation, cross-business-unit collaborations). In theorizing the CATS model, a new level of analysis was implemented, the interactions between agents as a move toward emergence in complex systems. The CATS model ultimately provides a model for organizations/institutions to drive knowledge creation and innovation while operating in today’s complexity.",signatures:"John R. Turner, Rose M. Baker and Kerry Romine",downloadPdfUrl:"/chapter/pdf-download/68710",previewPdfUrl:"/chapter/pdf-preview/68710",authors:[{id:"211379",title:"Dr.",name:"John",surname:"Turner",slug:"john-turner",fullName:"John Turner"},{id:"211381",title:"Dr.",name:"Rose",surname:"Baker",slug:"rose-baker",fullName:"Rose Baker"},{id:"309054",title:"MSc.",name:"Kerry",surname:"Romine",slug:"kerry-romine",fullName:"Kerry Romine"}],corrections:null},{id:"67115",title:"The Digitization in the Spanish Publishing Industry",doi:"10.5772/intechopen.86238",slug:"the-digitization-in-the-spanish-publishing-industry",totalDownloads:841,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The purpose of this chapter is to analyze the impacts of technological change in the Spanish publishing industry and see how it is adapting to the new digital environment. This work provides a deep insight into the Spanish publishing industry through the collection of available data, mainly from secondary sources of information, both public and private, and from a review of a great number of documents from different sources, grouping all the data obtained to generate a time series, allowing to glimpse the state and evolution of digitization in the Spanish publishing industry along these almost 20 years. This chapter refers to the new business models emerging from digitalization, ending with some conclusions, recommendations, and future lines of research. This chapter is not just trying to be a journey through the past, present, and future of the book industry in Spain, but it pretends being the first step to continue investigating these and other aspects in a deeper way.",signatures:"Marta Magadán-Díaz and Jesús Rivas-García",downloadPdfUrl:"/chapter/pdf-download/67115",previewPdfUrl:"/chapter/pdf-preview/67115",authors:[{id:"298449",title:"Dr.",name:"Marta",surname:"Magadán-Díaz",slug:"marta-magadan-diaz",fullName:"Marta Magadán-Díaz"},{id:"298450",title:"Dr.",name:"Jesús I.",surname:"Rivas",slug:"jesus-i.-rivas",fullName:"Jesús I. Rivas"}],corrections:null},{id:"70045",title:"Islamic Leadership: Comparisons and Qualities",doi:"10.5772/intechopen.90151",slug:"islamic-leadership-comparisons-and-qualities",totalDownloads:2959,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:1,abstract:"This chapter explores the concept and principles Islamic leadership which generate qualities. These qualities differentiate the Islamic leadership with other leadership concepts. The fundamental sources of Islamic leadership and guidance for the Muslim leaders are Al-Qur’an and Hadith. The sub-topics related to the Islamic leadership elaborate all attributes (traits, skills, power, authority) needed by the leaders. This content analysis method is based on a review of literature and other secondary data. The information in this chapter expectedly will give understanding on the importance of the Islamic leadership concept and can be useful or as a reference for further studies.",signatures:"Ahmad Rafiki",downloadPdfUrl:"/chapter/pdf-download/70045",previewPdfUrl:"/chapter/pdf-preview/70045",authors:[{id:"307090",title:"Ph.D.",name:"Ahmad",surname:"Rafiki",slug:"ahmad-rafiki",fullName:"Ahmad Rafiki"}],corrections:null},{id:"67541",title:"Digitalizing South African Universities: Exploring Benefits, Barriers and Risks",doi:"10.5772/intechopen.86693",slug:"digitalizing-south-african-universities-exploring-benefits-barriers-and-risks",totalDownloads:971,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"University leaders in South Africa have employed various leadership styles which focus on improving employee, departmental, faculty and organizational performance. However, digital leadership style is not popular and applied by leaders in universities in South Africa despite compelling benefits associated with digital leadership in universities which include improvement in communication with the key university stakeholders, enhancing the learning and teaching process, quality research outputs, community engagement, leadership and management. The present study aims to provide an understanding of the digital leadership in relation to other seminal leadership approaches which are pertinent in universities. This study further ascertains the benefits, challenges and risks in digitalizing campuses in the epoch of the Fourth Industrial Revolution. It significantly shapes university policies on digital technology, practices and theories on leadership styles which can bring radical changes in universities. This chapter equips university leaders to harness digital leadership style benefits and capacitate university leaders on risks associated by leading with technology. Application of the digital leadership style will assist university leaders in different employment categories to digitally improve employee and organizational performance, eliminate wastage and provide smooth communication channels and regular feedback.",signatures:"Bethuel Sibongiseni Ngcamu",downloadPdfUrl:"/chapter/pdf-download/67541",previewPdfUrl:"/chapter/pdf-preview/67541",authors:[{id:"282426",title:"Dr.",name:"Bethuel Sibongiseni",surname:"Ngcamu",slug:"bethuel-sibongiseni-ngcamu",fullName:"Bethuel Sibongiseni Ngcamu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5396",title:"Entrepreneurship",subtitle:"Practice-Oriented Perspectives",isOpenForSubmission:!1,hash:"297a3f7f82b2fba856f51501cf3e6864",slug:"entrepreneurship-practice-oriented-perspectives",bookSignature:"Mario 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In AF, atrial pumping ends, and blood tends to pool in the left atrium rather than be pumped into the left ventricle. Thrombi can form in the sluggish blood pool in the atrial region known as the left atrial appendage (LAA). A typical LAA thrombus can cause stroke or peripheral embolism should it break free. Indeed, AF-related strokes tend to be more life-threatening than strokes caused by other reasons [1].
\nAnticoagulation therapy prevents strokes and warfarin; the most commonly used vitamin K antagonist (VKA) has been the standard agent used to reduce stroke risk in certain AF patients with risk factors since the 1950s [2]. Historically, warfarin has been the drug of choice, but it has often been underused due to its narrow risk-benefit interval and the need for frequent monitoring. It is being gradually eclipsed by a variety of non-vitamin-K antagonist oral anticoagulants (NOACs) that are demonstrating excellent safety and effectiveness without the need for frequent monitoring and subsequent dose adjustment.
\nThe availability of several pharmacological approaches to anticoagulation as well as a more thorough understanding of risk factors for embolization and bleeding has improved patient care but also complicated prescribing choices. The paradigm for anticoagulation in AF patients has changed. In addition, there are now options for patients that suffer from AF but who, for one reason or another, are unable to take anticoagulants. These patients can often undergo closure of the LAA, the site of the majority of the thrombi.
\nThe distinction between valvular and nonvalvular AF is not helpful in terms of defining the nature of the arrhythmia, but it may be of value in better defining the patient’s risk for thromboembolism and which type of anticoagulation therapy (if any) is indicated [3]. AF may be paroxysmal or persistent, for example, or symptomatic or asymptomatic (“silent”). When decisions concerning anticoagulation are to be reached, the main factors that may affect prescribing choices are valvular versus nonvalvular forms of AF. Moreover, it should be noted that patients with nonvalvular AF may have concomitant valvular heart disease.
\nIn 2016, the European Society of Cardiology (ESC) defined nonvalvular AF as an exclusion of moderate to severe mitral valve stenosis or metallic prosthetic heart valves [4]. The American Heart Association (AHA) and American College of Cardiology (ACC) went a bit further in the exclusion and stated nonvalvular AF was AF not associated with rheumatic mitral stenosis, metallic or bioprosthetic heart valves, or mitral valve repair [5]. It has even been stated by experts that perhaps the terms “nonvalvular” and “valvular” AF are outmoded and no longer useful. See \nTable 1\n.
\nSociety or source | \nDefinition of valvular AF | \nDefinition of nonvalvular AF | \n
---|---|---|
American College of Cardiology Expert Consensus 2017 [6] | \nAF associated with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair | \nAll AF not associated with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair | \n
American College of Chest Physicians 2018 [7] | \nModerate to severe mitral stenosis or mechanical heart valve | \nAF not associated with moderate to severe mitral stenosis or mechanical heart valve | \n
Canadian Cardiovascular Society 2016 [8] | \nRheumatic mitral stenosis, mitral valve repair, mechanical or bioprosthetic heart valve | \nAF not associated with mitral stenosis, mitral valve repair, and mechanical or bioprosthetic heart valve | \n
Canadian Cardiovascular Society 2018 [9] | \nRheumatic mitral stenosis, moderate to severe non-rheumatic mitral stenosis, or mechanical heart valve | \nAF not associated with rheumatic mitral stenosis, moderate to severe non-rheumatic mitral stenosis, or mechanical heart valve | \n
De Caterina, Camm (Expert Opinion) 2016 [10] | \nProposes the use of “mechanical and rheumatic mitral AF” or MARM-AF as alternative | \nAF not associated with mechanical and rheumatic mitral AF | \n
European Heart Rhythm Association and European Society of Cardiology Working Group on Thrombosis 2017 [11] | \nThe term is outdated and should be replaced by a functional Evaluated Heartvalves, Rheumatic or Artificial (EHRA) category, based on the anticoagulation therapy used. EHRA typically is described as Types 1 and 2 Type 1 is valvular heart disease requiring VKA anticoagulation Type 2 is valvular heart disease requiring VKA or NOAC therapy | \n|
European Society of Cardiology 2016 [4] | \nAvoids the term, preferring “AF related to hemodynamically significant mitral stenosis or prosthetic mechanical heart valves” | \nAF not related to hemodynamically significant mitral stenosis or prosthetic mechanical heart valves | \n
National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand 2018 [12] | \nModerate to severe mitral stenosis or mechanical heart valve | \nAF not associated with moderate to severe mitral stenosis or mechanical heart valve | \n
UMBRIA-Fibrillazione Atriale Study (Clinical Trial) 2019 [13] | \nFavors the term Type 2 valvular heart disease, defined as moderate to severe mitral or aortic regurgitation, moderate to severe aortic stenosis, or mild mitral stenosis (mitral valve areas >2.0 cm2 on echocardiography) | \nAF not associated with moderate to severe mitral or aortic regurgitation, moderate to severe aortic stenosis, or mild mitral stenosis | \n
The definitions for nonvalvular and valvular AF, which can be crucial to selecting appropriate anticoagulation therapy, are blurred and may even be outmoded. Note that some guidelines did not define these terms at all.
Anticoagulation therapy helps to mitigate the risk of stroke in patients with nonvalvular forms of AF [14]. As such, anticoagulation may be indicated for patients with nonvalvular AF, but other factors may come into play. Surgery can affect the anticoagulation decision, both in terms of whether the AF patient needs anticoagulation therapy before and after surgery or just perioperatively for a short window of time [6].
\nAs seen in \nTable 1\n, valvular heart disease encompasses such conditions as mitral stenosis, mitral regurgitation, aortic stenosis, and aortic insufficiency. Valvular heart disease has an age-dependent prevalence of about 0.7% for 18–44-year-olds and 13.3% in patients ≥75 years, and it is considered a risk factor for stroke and systemic embolism. Valvular heart disease may coexist with arrhythmias, including AF [15]. Prosthetic heart valves are associated with thrombin growth, and heart valve surgery may expose the blood pool to mechanical hardware, both of which may activate intrinsic coagulation pathways. Valvular AF has been associated with platelet activation, which may contribute to further thromboembolic risk [3]. Since patients with mechanical heart valves were considered to be at risk for thromboembolism, they should always be prescribed with VKA for anticoagulation as no data exist for the use of NOAC in this subgroup [13]. Distinguishing characteristics for valvular and nonvalvular heart diseases appear in \nTable 2\n.
\nAspects of heart disease | \nValvular heart disease Type 1 | \nValvular heart disease Type 2 | \nNonvalvular AF | \nComments | \n
---|---|---|---|---|
Aortic regurgitation | \n\n | Yes | \n\n | \n |
Aortic stenosis | \n\n | \n | Yes | \nHigh risk for stroke | \n
Mechanical heart valve | \nYes | \n\n | \n | High risk for thromboembolism | \n
Mild mitral stenosis | \n\n | Yes | \n\n | \n |
Mitral regurgitation | \n\n | Yes | \n\n | Common form of valvular heart disease | \n
Moderate to severe aortic stenosis | \n\n | \n | Yes | \n\n |
Moderate to severe mitral stenosis | \nYes | \n\n | \n | May be of rheumatic origin | \n
An overview of distinguishing characteristics for valvular heart disease (Types 1 and 2) versus nonvalvular heart disease [13].
AF is a prevalent condition and occurs in many patient subpopulations that merit a short discussion in terms of anticoagulation and AF classification.
\nTranscatheter aortic valve replacement (TAVR) is often recommended for low-risk patients with severe symptomatic aortic stenosis, but less is elucidated about the role of postsurgical anticoagulation therapy in this population [16]. TAVR candidates have a 40% rate of pre-existing AF and a further 10% chance of developing new-onset AF following TAVR [17]. Most patients discharged following TAVR (n = 16,694) are on dual antiplatelet therapy without anticoagulation (81.1%) [18].
\nIn a study of 172 patients who underwent TAVR plus a pacemaker implant, 25% of the patients developed new-onset AF or atrial flutter over the median follow-up period of 15 months. Of these patients, 14.7% had at least an episode of asymptomatic AF, which was detected by device diagnostics in the pacemaker but not on their electrocardiogram (ECG). The cumulative incidence of stroke in this population was 1.4% for patients in normal sinus rhythm compared to 12.5% for new-onset AF patients. Patients with obvious AF, detected on ECG, were significantly more likely to be given anticoagulation therapy than those with subclinical new-onset AF (70% vs. 15%, respectively, p = 0.02) [19]. The rate and characteristics of AF in this particular patient population as well as those with new transcatheter aortic valve implantation (TAVI) are not extensively studied.
\nPatients undergoing catheter ablation for AF typically receive perioperative anticoagulation treatment that is discontinued following surgery providing they have no other risk factors. In the Role of Coumadin in Preventing Thromboembolism in AF Patients Undergoing Catheter Ablation (COMPARE) study, it was shown that continuing warfarin for 48 hours after the procedure was associated with fewer periprocedural strokes and fewer minor bleeding events compared to bridging using low-molecular-weight heparin [20].
\nResults are mixed in terms of the safety and effectiveness of warfarin versus newer agents. In a prospective cohort of 290 AF ablation patients, periprocedural administration of dabigatran compared to warfarin was associated with a higher rate of thromboembolic events (2.1% vs. 0.0% for dabigatran and warfarin, respectively) and major bleeding complications (6% vs. 1%, p = 0.019) [21]. However, in a case-control analysis of 763 patients undergoing radio-frequency AF ablation, dabigatran patients had similar anticoagulation effectiveness and safety compared to warfarin patients [22]. A meta-analysis of 14 studies on the use of dabigatran vs. warfarin for periprocedural anticoagulation in patients undergoing catheter ablation for AF (n = 4782) reported dabigatran patients had a similar incidence of major bleeding events and thromboembolic events compared to warfarin patients, and both agents were associated overall with low rates of complications [23].
\nNOACs have been evaluated in patients undergoing catheter ablation for AF. In the RE-CIRCUIT, it was shown that uninterrupted dabigatran is associated with fewer bleeding complications than uninterrupted warfarin in this population [24]. The AXAFA-NET 5 trial found that continuous apixaban is safe and effective following catheter ablation to treat AF in terms of bleeding, stroke, and cognitive function [25]. Uninterrupted rivaroxaban was shown to be feasible in this population with event rates similar to that of uninterrupted VKA [26].
\nIn some cases, patients on anticoagulation therapy are subsequently indicated for implantation of a cardiac implantable electronic device (CIED). In a randomized study of patients undergoing implantation of an implantable cardioverter defibrillator (ICD), 343 patients were randomized either to undergo bridging to heparin during the procedure or to be continued on warfarin. Major thromboembolic complications in this study were rare and similar between groups (the heparin patients reported one case of cardiac tamponade and one case of myocardial infarction, while the warfarin group had one transient ischemic attack). Device pocket hematoma of clinical significance occurred in 3.5% of warfarin patients compared to 16.0% of heparin patients [27].
\nThe prevalence of asymptomatic or “clinically silent” (subclinical) AF is unknown but likely substantial [28]. Clinically silent AF is often captured by device diagnostics in CIED patients. In a study of dual-chamber pacemaker patients (411 without known AF and 267 with known AF), it was found that at a median 38 months of follow-up, 30% of those without known AF had silent AF verifiable by the pacemaker. Risk factors for silent AF in this study were heart failure (p = 0.03) and age > 75 years (p = 0.0002). Sixty-two percent of patients who developed silent AF (n = 125) were administered with anticoagulation therapy; of those with known AF at implant (n = 216), 80% took anticoagulation therapy. The annual rate of stroke was 1.9% for patients who developed silent AF postimplant compared to 2.1% for those with known AF at implant. Vascular dementia developed in 11.2% of those with known AF at implant compared to 6.2% of those who developed silent AF postimplant (p = 0.048) [29].
\nSilent stroke may be defined as asymptomatic cerebral infarction, which is typically discovered when brain lesions are found during imaging procedures. Indeed, silent stroke is one of the most common incidental findings in brain scans [30]. The incidence and prevalence of this condition is not known nor are risk factors, although it appears that patients with AF are at elevated risk compared to those without this arrhythmia [31, 32]. The role of anticoagulation for patients at risk for silent stroke is not clear [30].
\nThe goal of anticoagulation therapy in AF patients is to reduce their risk for stroke or systemic embolism. The CHA2DS2-VASc scoring system has been developed to calculate the numerous factors that may increase the likelihood of thrombus: hypertension, heart failure, older age, diabetes, stroke, transient ischemic attack, vascular disease, and female sex [5, 33]. For patients who score ≥ 1 on this scoring metric, oral anticoagulation therapy is preferred over antiplatelet therapy. However, scoring tools are imperfect. A large retrospective review of 140,420 AF patients found the annual rate for ischemic stroke with those scoring ≤1 was lower than previously stated (0.1–0.2% for women and 0.5–0.7% for men) [33]. A retrospective cohort study found that age between 65 and 74 years was a stronger predictor of stroke compared to the other items on the CHA2DS2-VASc scoring system. People in that age bracket had an annual stroke risk of 1.78%. By the same token, AF patients <50 years of age had low risk (0.53%) [34].
\nHemostatic alteration introduces the risk of potentially devastating bleeding, typically intracranial hemorrhage [35]. The consequences of a bleeding event are of greater clinical importance than the amount of bleeding itself, for instance, a small amount of pericardial bleeding following cardiac surgery may have potentially life-threatening consequences, while a much larger bleeding event may be clinically manageable. Bleeding is a high-risk situation and is not the subject of clinical trials. In fact, most of the evidence about bleeding rates and risks is derived from safety reports in clinical trials. Thus, expert consensus often overrides data-driven evidence in terms of bleeding risks.
\nIn addition to procedure-related bleeding risks, individual patient factors for bleeding must also be taken into account. The HAS-BLED score, based on a survey of almost 4000 patients in the Euro Heart Survey on AF, offers a way to create a numerical score based on several factors. The acronym encapsulates some of the key risks: hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years), and drugs and/or alcohol concomitantly [36]. The HAS-BLED has seen a wide adoption, but two important points must be considered. Firstly, many risk factors in the HAS-BLED score are shared with other risk-scoring schemes for calculating the risk of thrombosis, e.g., hypertension and stroke. Secondly, a high HAS-BLED score is not necessarily indicative that oral anticoagulation should be omitted but may be used to select patients in need for regular follow-up.
\nFor over half a century, the anticoagulation regimen for AF was the use of VKA, also called coumarins. They included acenocoumarol, phenprocoumon, fluindione, and warfarin [37]. Warfarin is by far the most common of these and is the most commonly used anticoagulant [38]. These are effective agents, but they have certain disadvantages: a narrow therapeutic range, required laboratory monitoring, good patient adherence for safety and effectiveness, and certain risks for drug-drug and drug-food interactions [39].
\nThe emergence of NOAC drugs has changed the paradigm for anticoagulation therapy. These agents have been shown noninferior to warfarin with respect to thromboembolism. They may alleviate some of the disadvantages of VKA anticoagulation, but some of them do not have reversal agents. A short summary of anticoagulants appears in \nTable 3\n.
\n\n | Apixaban | \nDabigatran | \nEdoxaban | \nRivaroxaban | \nWarfarin | \n
---|---|---|---|---|---|
Dosing | \n5 mg × 2 but 2.5 mg × 2 if two of the following: age > 80 years, weight < 60 kg, or creatinine >133 μmol/l | \n150 mg × 2 or 110 mg × 2 if either: age > 80 h, GFR 30–50 ml/min, GI disease, increased risk of bleeding | \n60 mg × 1 but 30 × 1 if one of the following: weight ≤ 60 kg, concomitant ciclosporin, dronedarone, erythromycin, ketoconazole | \n20 mg × 1 but 15 mg × 1 if GFR 15–50 ml/min | \nStrat dose 5–7.5 mg, daily, and then adjustment to INR | \n
Renal failure | \nContraindicated | \nContraindicated | \nContraindicated | \nContraindicated | \nApproved indication | \n
Risk of intracranial bleeding vs. warfarin | \nLower | \nLower | \nLower | \nLower | \n— | \n
Interactions with other drugs or food | \nFew | \nFew but note dronedarone | \nFew | \nFew | \nNumerous | \n
Possible to crush tablet | \nYes | \nNo | \nYes | \nYes | \nYes | \n
Independent of timing of food intake | \nYes | \nYes | \nYes | \nNo | \nYes | \n
Laboratory follow-up | \n6–12 months | \n6–12 months | \n6–12 months | \n6–12 months | \nFrequent, typically 1–2 every month | \n
Specific antidote | \nNo | \nYes, instant effect | \nNo | \nNo | \nYes, slow effect | \n
A short summary of anticoagulation agents.
Vitamin K antagonists (VKA) act by reducing the synthesis of the coagulation factors that rely on vitamin K. They inhibit the liver’s ability to synthesize the precursors to clotting factors, Factor II (prothrombin), Factor VII, Factor IX, and Factor X. For that reason, it may take up to 2 weeks before all of these factors are eliminated and the drug is effective [35]. Warfarin may be reversed with oral or intravenous vitamin K, although the reversal may take hours to take effect [40]. Warfarin is an effective anticoagulant as long as blood concentrations fall within a relatively narrow therapeutic range; regular monitoring for time in therapeutic range is required. There is a wealth of clinical experience with VKA to inform prescribing choices.
\nAlthough warfarin may seem to be eclipsed by newer and more convenient agents, warfarin is still frequently prescribed and may be the optimal choice for some patients. VKA anticoagulation therapy decreases the risk of ischemic stroke in AF patients by >60%, although it does present a slightly increased risk for bleeding (<0.3%/year) [41].
\nPrescribing considerations for warfarin must include its narrow therapeutic index (overdosing may cause bleeding, and underdosing may cause thrombosis). Thus, warfarin patients must be followed with regular assessment of their international normalized ratio (INR). While genetics influence how an individual responds to VKA, such tests are not often used, and there is little guidance in terms of how to apply the findings from such genetic tests to therapeutic choices [42, 43]. Warfarin can be monitored at home with a home-based system and weekly test strips. The direct cost of warfarin is lower than for NOAC medications.
\nAn important safety concern about warfarin involves hemorrhagic stroke which may occur in patients on VKA therapy. In fact, about 12–14% of cases of intracerebral hemorrhage are associated with warfarin [44]. VKA agents appear to contribute to vascular calcification to a greater extent than NOACs [45]. Drug-drug or food-drug interactions often occur with VKA therapy, particularly involving foods and drugs that induce or inhibit the CYP 450 enzymes [39, 46].
\nFour NOAC medications are approved and indicated for stroke prevention in patients with nonvalvular AF in the USA with some international variations. The NOAC category offers drugs in two classes: those that inhibit Factor Xa (apixaban, edoxaban, rivaroxaban) and direct thrombin inhibitors (dabigatran). Trials have demonstrated they are effective anticoagulation options with reasonable safety profiles. The advantages of NOACs compared to VKA therapy include predictable pharmacokinetics, rapid onset and offset of action, recent promising evidence from clinical trials showing reductions in stroke, intracranial hemorrhage, and all-cause mortality [46]. NOACs offer advantages, but the lingering concern with such medications is the lack of a reversal agent to stop the anticoagulatory effect in the event of a bleeding emergency for all these agents except dabigatran. The monoclonal antibody idarucizumab is available as a specific, with rapid onset, reversal agent for dabigatran [47].
\nApixaban is a highly selective direct inhibitor of activated coagulation Factor X that can indirectly inhibit thrombin-induced platelet aggregation. It is an oral anticoagulant with linear and predictable pharmacokinetics and rapid onset/offset of action and has relatively few potential drug-drug or drug-food interactions [48]. In a meta-analysis of 16 studies, apixaban was more effective in reducing the rate of thromboembolic events compared to warfarin but similar to warfarin in reducing the risk of stroke [49]. However, it may reflect patient selection, and it is important to stress that no head-to-head studies with a randomized controlled have been conducted.
\nA post hoc analysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study compared clinical characteristics and outcomes in AF patients with a history of cancer taking either apixaban or warfarin. The outcomes were stroke, systemic embolism, major bleeding, and mortality [50]. In the study, 157 patients had active cancer, the remaining 1079 had remote cancer, and they were compared to 16,947 patients without cancer. No significant relationships between cancer and stroke, systemic embolism, ischemic stroke, or death could be determined, and the relationship between cancer and myocardial infarction was not significant after statistical adjustment. Apixaban was associated with improved rates of the composite endpoint (stroke, systemic embolism, myocardial infarction, and mortality) in those with active cancer and in those without cancer but not in those with remote cancer [50]. In a post hoc analysis of the ARISTOTLE study, 76.5% of patients were found to be on polypharmacy, defined as ≥5 or more drugs, and mortality, stroke, and systemic embolism rates increased with the greater number of concomitant medications [51]. Apixaban was deemed to be more effective than warfarin in AF patients on polypharmacy compared to warfarin and at least equivalent in terms of safety. An analysis of ARISTOTLE study data found 104 patients had a bioprosthetic heart valve replacement, and 52 had undergone valve repair. The safety and effectiveness of apixaban in this subpopulation was consistent with the larger study results, that is, apixaban may be an appropriate choice for a patient with valve replacement or repair [52]. Using data from this study, it was found that 30.5% of patients were taking potentially interacting medications at the time of the study (2722 apixaban and 2824 warfarin patients), which is common among AF patients. For the primary outcome endpoint (stroke or systemic embolism), both apixaban and warfarin were similar, and interacting medications had no effect on this outcome [53]. Apixaban results were also consistent in the multimorbid population (64% of ARISTOTLE population, defined as ≥3 comorbid conditions); apixaban was similarly effective in the general ARISTOTLE population as in the multimorbid subpopulations, including those with high multimorbidity (≥6 comorbid conditions) [54].
\nUsing a Markov model and a population model from 2017 to 2030, apixaban was compared to warfarin in the German population of nonvalvular AF patients. The study showed that apixaban use instead of a VKA could avoid 52,185 major clinical events, including 14,319 all-cause deaths and 15,383 nonfatal strokes [55]. A Department of Defense study in the USA (n = 41,001) found apixaban was associated with a significantly lower risk of stroke, systemic embolism, or major bleeding compared to warfarin and to rivaroxaban [56].
\nDabigatran, a prodrug, is a direct thrombin inhibitor with predictable pharmacokinetics and pharmacodynamics, no need for laboratory monitoring, and fewer drug-food and drug-drug interactions compared to VKA. Unlike other NOAC drugs, dabigatran has an approved specific reversal agent, idarucizumab [57]. Dabigatran holds the distinction of being the first NOAC agent to be approved for nonvalvular AF patients [58].
\nThe Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study (n = 18,113) compared dabigatran at two doses (150 or 110 mg twice a day) to warfarin in a trial of AF patients that excluded those with mechanical heart valves, moderate to severe mitral stenosis, or valvular heart disease requiring intervention (patients with valvular heart disease not requiring intervention could be included) [59]. For dabigatran 150 mg twice daily, the rate of stroke or systemic embolic events was significantly lower than that of patients taking warfarin, but for those on 110 mg twice daily, rates were similar to warfarin. Intracranial bleed rates and mortality rates were significantly lower in both dabigatran groups compared to warfarin regardless of whether or not the patient had valvular heart disease [59].
\nThe randomized phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN) study was terminated early when it compared VKA therapy to dabigatran and the dabigatran group experienced a high rate of thromboembolic and bleeding adverse events [60]. The study enrolled patients undergoing atrial and/or mitral mechanical valve implantation who were administered with 150 or 300 mg of dabigatran twice a day to determine relative safety and effectiveness of dabigatran compared to warfarin [61]. Dabigatran patients experienced higher rates of adverse events: 5% had strokes, 2% transient ischemic attacks, and 2% myocardial infarction compared to only transient ischemic attacks only at a rate of 2% in the warfarin group. The reasons for this have been speculated: dabigatran doses were too high, dabigatran was introduced too soon after valve surgery, or there remain factors to be elucidated about thromboembolic risks associated with artificial heart valves [62].
\nEdoxaban, a factor Xa inhibitor, is approved for the prevention of stroke in nonvalvular AF patients. Factor Xa is a protease that serves to convert prothrombin into thrombin which, in turn, converts fibrinogen into fibrin and allows for clotting. Edoxaban has a dual mechanism of action in that it inhibits both free Factor Xa and also the by-product Factor Xa produced by prothrombinase [63]. Like other NOAC medications, it requires less laboratory monitoring, has fewer drug-drug and food-drug interactions, and lowers the risk of major bleeding compared to warfarin. It is not metabolized via the CYP450 enzyme system (which is the case for apixaban and rivaroxaban), and it was shown in the ENGAGE AF-TIMI study to be noninferior to warfarin. It is an oral agent that need be taken only once daily [63]. The safety and efficacy of edoxaban seem to be similar to other NOAC medications for the control of venous thromboembolism to reduce the risk of stroke in nonvalvular AF patients.
\nThe Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombosis in Myocardial Infarction 48 study (ENGAGE-AF-TIMI 48) compared edoxaban to warfarin in AF patients with and without valvular heart disease [64]. Valvular heart disease is associated with an increased risk for major adverse cardiovascular events, major bleeding, and death. Higher-dose edoxaban was found to be similarly effective to warfarin for all endpoints (stroke, systemic embolic event, major bleeding) in a trial of 18,222 patients [64].
\nA substudy of ENGAGE AF-TIMI 48 examined the effect of patient age on bleeding risk (risk is greater with older age) and favored edoxaban over warfarin for AF patients ≥75 years [65]. As such, edoxaban may be preferred over warfarin in elderly patients at risk for falls [66].
\nRivaroxaban is an NOAC that acts as a selective, direct inhibitor of activated coagulation Factor Xa. It is an oral medication with a rapid onset/offset of action and short half-life. It does not require laboratory monitoring and has predictable pharmacokinetics and pharmacodynamics and relatively few drug-drug and drug-food interactions compared to warfarin [67]. There is currently no approved reversal agent for rivaroxaban.
\nThe ROCKET-AF study (n = 14,264) compared rivaroxaban to warfarin and found rivaroxaban had a 1.7% risk of stroke or systemic embolism at 1 year compared to 2.2% for warfarin. The composite safety endpoint was major bleeding or major bleeding plus clinically relevant non-major bleeding and occurred at a rate of 14.9% for rivaroxaban and 14.5% for warfarin patients [68]. The study concluded that rivaroxaban was noninferior to warfarin in prevention of stroke and systemic embolism. There was no significant difference in major or non-major but clinically relevant bleeding between rivaroxaban and warfarin. Gastrointestinal bleeding occurred more often in rivaroxaban than warfarin patients, but rates of major bleeding were similar.
\nThere may be cases when it becomes necessary to change from warfarin to an NOAC or vice versa. In the case of moving from VKA to an NOAC, INR monitoring is needed throughout the shift [14]. The opposite transition, from NOAC to VKA, may require bridging to heparin or starting off with a lower dose of the NOAC medication at first, INR twice a week (minimum), and adjustment of VKA until the INR reaches ≤2.0 [69].
\nIn an elderly population (262,611 patients ≥60 years free of dementia and stroke), it was observed that incident AF was associated with an increased risk of dementia independent of stroke, while anticoagulation therapy decreased the risk for dementia [70]. The association between AF and dementia is not well elucidated, but white matter lesions, silent brain infarcts, and microbleeds in the brain are more common in AF patients, and it is not clear whether anticoagulation might play a role in this decreased risk for dementia [71].
\nPatients with liver disease are at risk for increased bleeding with anticoagulation therapy (but not increased thromboembolic events) [72]. However, NOAC therapy was shown in a clinical study (n = 39) to be safe and effective in cirrhosis patients [73].
\nWarfarin is teratogenic and should not be administered to pregnant women or women of childbearing potential without a clear understanding that they must not get pregnant while taking this drug [74].
\nNOAC anticoagulation offers advantages over VKA anticoagulation but also poses new challenges in the management of emergency situations. Emergency thrombolysis for treatment of ischemic stroke requires that the coagulation system be intact and, for this reason, is contraindicated in patients taking NOAC drugs, unless the agent is completely reversed before [75]. Prothrombin time and other laboratory tests are often faster and easier to accomplish with VKA therapy than NOAC in emergencies. For major bleeding events, rapid reversal of anticoagulation may be required which is likewise easier with VKA; however, reversing VKA agents such as warfarin may still take hours. Among the NOAC options, only dabigatran has a reversal agent, while the reversal agents for the other NOAC medications are in development.
\nThe NOAC medications and warfarin have been the subject of large published clinical trials, but head-to-head studies among the NOACs have not yet been carried out, and attempts to analyze data across trials have been challenged by differences in study methodologies, the AF populations evaluated, definitions (stroke, AF, major bleeding, and so on), and composite endpoints [76]. A meta-analysis (n = 17 studies) comparing rivaroxaban, dabigatran, and warfarin in real-world settings found that rivaroxaban was similar to warfarin in terms of the risks for major bleeding, myocardial infarction, and all-cause mortality; rivaroxaban was associated with a lower risk for stroke or systemic thromboembolism compared to warfarin; however, rivaroxaban had a higher risk for gastrointestinal bleeding than warfarin. Compared to dabigatran, rivaroxaban had similar risks for stroke and systemic thromboembolism and myocardial infarction, but the risks for major bleeding, gastrointestinal bleeding, and all-cause mortality were higher with rivaroxaban than dabigatran [77]. A retrospective study found that rivaroxaban and apixaban elevate the INR to levels above the high cutoff for normal (84.2% of rivaroxaban and 78.3% of apixaban with rivaroxaban significantly higher than apixaban, p < 0.001); however the clinical implications for these elevated INR values are not known [78].
\nA retrospective study of 1365 geriatric patients with head trauma found that NOAC therapy was a safer alternative than warfarin, although warfarin and NOACs were associated with similar mortality rates. NOAC patients had a lower rate of intracranial hemorrhage progression [79]. A retrospective database study of nonvalvular AF patients newly started on rivaroxaban, apixaban, or warfarin matched 11,411 rivaroxaban users to 11,411 warfarin patients and reported that the risk of ischemic stroke or intracranial hemorrhage was significantly lower in the rivaroxaban patients than in the warfarin patients. The study further matched 4083 apixaban patients to 4083 warfarin patients and found the combined endpoint (ischemic stroke or intracranial hemorrhage) was nonsignificantly reduced by apixaban versus warfarin. Apixaban reduced the risk of intracranial hemorrhage (hazard ratio 0.38, 95% confidence interval, 0.17–0.88) compared to warfarin, but the risk of ischemic stroke was nonsignificantly increased by apixaban versus warfarin (hazard ratio 1.13, 95% confidence interval, 0.49–2.63). The study did not compare rivaroxaban to apixaban [80].
\nIn a study of 962 consecutive TAVR patients prescribed with NOAC (n = 326) or VKA therapy (n = 636) after surgery, the composite study endpoint were all-cause mortality, myocardial infarction, and any cerebrovascular event. After 1 year of follow-up from TAVR, the composite endpoint occurred in 21.2% of NOAC and 15.0% of VKA patients. Rates of bleeding and all-cause mortality were similar, but NOACs had a higher rate of ischemic events than VKA therapy [81]. In a systematic review of anticoagulation therapy in AF patients with valvular heart disease and bioprosthetic heart valves, edoxaban 30 mg was associated with the least rate of major bleeding compared to rivaroxaban, VKA, and other similar agents. Overall, NOAC medications were more effective in this population than warfarin, and NOACs were similar with the exception of edoxaban and major bleeding rates [82].
\nEvidence from clinical trials shows promise but does not yet provide clinicians with a complete picture. For example, patients with moderate to severe mitral stenosis or those with a mechanical heart valve are both at elevated risk from thromboembolism and typically excluded from head-to-head clinical trials that compare VKAs to specific NOACs. There are also patient groups who have been included in some, but not other trials, for example, patients who had a previous heart valve surgery (but not a mechanical valve) were excluded from RE-LY but included in ROCKET-AF, ΑRISTOTLE, and ENGAGE-AF. Patients with AF and a mechanical heart valve are routinely excluded from most head-to-head trials on anticoagulation. Thus, there are gaps in the evidence as to which types of anticoagulation treatments are most effective in specific populations.
\nAlthough it is well known that anticoagulation therapy can help prevent stroke in AF patients at risk for thromboembolic events, only about half of the indicated patients actually are prescribed with therapy [83]. There is an inverse relationship between antiplatelet prescription and non-prescription of anticoagulation therapy. However, antiplatelet therapy is not as effective as anticoagulation medications for stroke prevention [84]. When prescribing anticoagulation therapy, the clinician must evaluate several factors: the indications for anticoagulation therapy, individual patient characteristics, whether or not the patient is taking other medications, patient preferences (if any), clinician and institutional preferences, and cost [14]. When antiplatelet therapy is combined with anticoagulation, the risk for bleeding increases [14]. Among patients with nonvalvular AF, those with heart failure and/or left-ventricular dysfunction have higher rates of bleeding and stroke/systemic embolism. Although some large trials of NOACs have included such patients, there have been no specific studies to investigate the safety of such drugs in these populations [85], and there is little evidence to guide prescribing choices.
\nComorbidities must be considered when selecting the optimal anticoagulation regimen for a specific patient. Hepatic disease may increase the patient’s risk for bleeding and impairs hepatic drug metabolism and clearance. In NOAC trials, patients with liver disease were excluded, so there is a paucity of evidence about how to use NOAC therapy in this population. A retrospective database study from Korea (12,778 warfarin patients and 24,575 NOAC patients) found NOACs reduced the risk for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and all-cause death compared to warfarin. In the 13% of this study population with active liver disease, there was a lower rate for the composite endpoint (all endpoints above) for NOAC than warfarin [86].
\nRenal failure, common in AF patients, has an inflammatory pathophysiology and puts patients at risk for both thromboembolitic events and bleeding [87]. Since NOACs are cleared by the kidneys, renal failure has an adverse effect on NOAC pharmacokinetics but not on warfarin. However, warfarin likewise can interact with other drugs including drugs taken by patients managing kidney disorders [88]. A retrospective database study in Germany, RELOAD, compared outcomes of nonvalvular AF patients with compromised renal function taking either rivaroxaban or phenprocoumon (VKA therapy) and found that for patients with no evidence of cancer, rivaroxaban was associated with a lower rate of ischemic stroke and intracranial hemorrhage compared to phenprocoumon [89]. Warfarin is also more commonly prescribed to nonvalvular AF patients on hemodialysis, and while no head-to-head clinical trials have compared warfarin to NOACs in this population, dialysis patients are sometimes prescribed with NOAC therapy. The preference for NOACs in the hemodialysis population may be due to several concerns: it is difficult to maintain warfarin at INR in the therapeutic range, warfarin may calcify vasculature, and dialysis patients have an elevated risk of intracranial hemorrhage. Hemodialysis patients are challenging for anticoagulation, because they often are multimorbid, have extensive antibiotic exposure, and may have vitamin K deficiency. Adherence can also be especially problematic in the hemodialysis population [90].
\nThe role of anticoagulation in cancer patients becomes complex as many cancer patients are at increased bleeding risk and may be taking antiplatelet agents and nonsteroidal anti-inflammatory drugs, have renal impairment, or be on chemotherapy. Many chemotherapeutic agents increase the patient’s risk of arterial and venous thrombosis, and chemotherapy that induces thrombocytopenia may elevate bleeding risks [91]. There is also the risk that anticoagulants may interact with chemotherapeutic agents or supportive-care drugs. Many chemotherapeutic regimens (cisplatin, melphalan, cyclophosphamide) and some monoclonal antibodies increase the risk of nonvalvular AF. Cancer patients with AF have an increased risk for thromboembolism [92]. There is only limited knowledge of the risk of ischemic stroke attributable to cancer, and many risk assessment tools do not incorporate cancer. Further, cancer is not just one disease, and there may be important clinical variations with respect to the type of cancer, AF risk, and risk of thromboembolism and stroke [93].
\nPatient factors may also influence prescribing choices. Patient adherence must be considered in long-term anticoagulation therapy; the continuously adherent rate is under 45% for those newly diagnosed AF patients prescribed with some form of anticoagulation therapy [94]. Patient education may play a role in improving adherence. In a study of 339 adults on anticoagulation treatment for nonvalvular AF, participants evidenced moderate knowledge about AF but had a more limited understanding of anticoagulation and stroke [95]. Thus, better educational efforts may be helpful. Culture and ethnicity may also be a consideration when making prescribing determinations. In a multinational survey of 937 adults on anticoagulation treatment for nonvalvular AF, national differences emerged such that US patients perceived AF as a serious condition, whereas the Japanese were less concerned about AF, but both were quite concerned about stroke risks. French patients preferred the physician to select AF therapy, while German, US, and Canadian patients preferred to be involved in therapeutic choices [96]. A cross-sectional survey of 226 physician specialists in Bulgaria also reports that 68% of patients who have an indication for anticoagulation therapy preferred a shared decision-making approach, and only 19% wanted the physician to make all anticoagulation therapy choices [97]. Improved understanding about the risk of stroke, the nature of stroke, and anticoagulation treatment may improve adherence and empower patients in their own care.
\nWomen taking warfarin have a greater risk of stroke/embolism than men, but this sex difference is not maintained for all of the NOACs [98]. Moreover, there is some evidence that with NOACs, women have less risk of major bleeding than men. The differences have been discussed in the literature and do not seem to apply to anticoagulation effectiveness [99]. Further studies are needed, but it appears that NOAC drugs may have some sex-based differences that at this time seem clinically unimportant.
\nSome patients have a relative or absolute contraindication to anticoagulation therapy. Device-based approaches may be important options for these patients. It exceeds the scope of this chapter to describe these devices, their implantation, and results in detail, but a brief introduction is offered. Direct closure of the LAA via a minimally invasive surgical procedure is well established. It is a safe, effective procedure that can generally be performed in 30–40 min. Initially, the LAA was closed utilizing an endoscopic stapler, but more recently a minimally invasive LAA surgical clip is used (AtriClip, AtriCure, Inc., Cincinnati, Ohio, USA). The clip offers complete closure immediately, and no postoperative anticoagulation is needed.
\nA device implanted under fluoroscopic control into the orifice of the LAA by transseptal puncture may also be used (Watchman, Boston Scientific, Inc., Boston, Massachusetts, USA). This device has a high leak rate, and the US Food and Drug Administration requires postoperative anticoagulation for several weeks after implantation. Five-year outcomes from two large randomized clinical trials (PREVAIL and PROTECT AF) found that LAA closure with the WATCHMAN device offered stroke prevention in patients with nonvalvular AF comparable to that of warfarin with additional reductions in major bleeding and mortality [100].
\nIn contrast to these is a suture-based occluding device (Lariat, SentreHEART, Redwood City, California, USA) that requires transseptal implantation. Unlike WATCHMAN, this device does in fact close the LAA, but in addition to a transseptal puncture, it requires access to the pericardium. A large randomized multicenter controlled trial is ongoing to determine the 30-day safety of this device and freedom from documented episodes of AF, atrial flutter, or atrial tachycardia >30 s at 12 months with a secondary composite endpoint of cardiovascular death or stroke [101].
\nNew anticoagulation therapies are changing the paradigm of anticoagulation treatment for patients with certain forms of AF. This shift is further complicated by the fact that the definition and understanding of nonvalvular versus valvular AF are under scrutiny and evolving. Vitamin K antagonism (warfarin and other drugs) had been the standard of care for decades and still represents an important anticoagulation option. The main drawbacks to VKA are the need for laboratory monitoring and strict therapy adherence to maintain anticoagulation efficacy plus the potential for drug-drug and food-drug interactions. A benefit for warfarin and other VKA treatments is the fact that the anticoagulation effect can be pharmacologically reversed. The arrival of the NOAC agents presents improved effectiveness in many key endpoints such as stroke prevention and similar or enhanced safety with respect to bleeding risks. There are four of these drugs (apixaban, dabigatran, edoxaban, and rivaroxaban), but as yet there are no head-to-head clinical trials among them for clinical guidance. Except for dabigatran, there are presently no reversal agents for these drugs. Clinicians must evaluate these anticoagulation approaches to make individualized decisions for patients. Further study is needed, particularly for specific subpopulations of AF patients: those with heart failure, implanted devices, renal compromise, and cancer.
\nPeter Magnusson has received speaker fees or grants from Abbott, Alylam, Bayer, AstraZeneca, BMS, Boeringer-Ingelheim, Lilly, Novo Nordisk, Octupus Medical, and Pfizer. Joseph Pergolizzi is a principal at Native Cardio, Inc. Randall K. Wolf is a paid consultant to the engineering team at AtriCure, Inc. Morten Lamberts has received speaker fees from BMS. Jo Ann LeQuang has no relevant disclosures.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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The possible interferences of atomic or molecular species are used to specify organic, inorganic or biological materials which allows critical applications in defense (landmines, explosive, forensic (trace of explosive or organic materials), public health (toxic substances pharmaceutical products), or environment (organic wastes). Laser induced plasma for organic material potentially provide fast sensor systems for explosive trace and pathogen biological agent detection and analysis. The laser ablation process starts with electronic energy absorption (~fs) and ends at particle recondensation (~ms). Then, the ablation process can be governed by thermal, non-thermal processes or a combination of both. There are several types of models, i.e., thermal, mechanical, photophysical, photochemical and defect models, which describe the ablation process by one dominant mechanism only. Plasma ignition process includes bond breaking and plasma shielding during the laser pulse. Bond breaking mechanisms influence the quantity and form of energy (kinetic, ionization and excitation) that atoms and ions can acquire. Plasma expansion depends on the initial mass and energy in the plume. The process is governed by initial plasma properties (electron density, temperature, velocity) after the laser pulse and the expansion medium. During first microsecond after the laser pulse, plume expansion is adiabatic afterwards line radiation becomes the dominant mechanism of energy loss.",book:{id:"5093",slug:"plasma-science-and-technology-progress-in-physical-states-and-chemical-reactions",title:"Plasma Science and Technology",fullTitle:"Plasma Science and Technology - Progress in Physical States and Chemical Reactions"},signatures:"Kashif Chaudhary, Syed Zuhaib Haider Rizvi and Jalil Ali",authors:[{id:"176684",title:"Dr.",name:"Kashif Tufail",middleName:null,surname:"Chaudhary",slug:"kashif-tufail-chaudhary",fullName:"Kashif Tufail Chaudhary"},{id:"176867",title:"Dr.",name:"Syed Zuhaib",middleName:null,surname:"Haider Rizivi",slug:"syed-zuhaib-haider-rizivi",fullName:"Syed Zuhaib Haider Rizivi"},{id:"176868",title:"Prof.",name:"Jalil",middleName:null,surname:"Ali",slug:"jalil-ali",fullName:"Jalil Ali"}]},{id:"52164",title:"An Overview on Quantum Cascade Lasers: Origins and Development",slug:"an-overview-on-quantum-cascade-lasers-origins-and-development",totalDownloads:3232,totalCrossrefCites:2,totalDimensionsCites:11,abstract:"This chapter presents an introductory review on quantum cascade lasers (QCLs). An overview is prefaced, including a brief description of their beginnings and operating basics. Materials used, as well as growth methods, are also described. The possibility of developing GaN-based QCLs is also shown. Summarizing, the applications of these structures cover a broad range, including spectroscopy, free-space communication, as well as applications to near-space radar and chemical/biological detection. Furthermore, a number of state-of-the-art applications are described in different fields, and finally a brief assessment of the possibilities of volume production and the overall state of the art in QCLs research are elaborated.",book:{id:"5389",slug:"quantum-cascade-lasers",title:"Quantum Cascade Lasers",fullTitle:"Quantum Cascade Lasers"},signatures:"Raúl Pecharromán-Gallego",authors:[{id:"188866",title:"Dr.",name:"Raúl",middleName:null,surname:"Pecharromán-Gallego",slug:"raul-pecharroman-gallego",fullName:"Raúl Pecharromán-Gallego"}]},{id:"49526",title:"Focused Ion Beams (FIB) — Novel Methodologies and Recent Applications for Multidisciplinary Sciences",slug:"focused-ion-beams-fib-novel-methodologies-and-recent-applications-for-multidisciplinary-sciences",totalDownloads:4299,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Considered as the newest field of electron microscopy, focused ion beam (FIB) technologies are used in many fields of science for site-specific analysis, imaging, milling, deposition, micromachining, and manipulation. Dual-beam platforms, combining a high-resolution scanning electron microscope (HR-SEM) and an FIB column, additionally equipped with precursor-based gas injection systems (GIS), micromanipulators, and chemical analysis tools (such as energy-dispersive spectra (EDS) or wavelength-dispersive spectra (WDS)), serve as multifunctional tools for direct lithography in terms of nano-machining and nano-prototyping, while advanced specimen preparation for transmission electron microscopy (TEM) can practically be carried out with ultrahigh precision. Especially, when hard materials and material systems with hard substrates are concerned, FIB is the only technique for site-specific micro- and nanostructuring. Moreover, FIB sectioning and sampling techniques are frequently used for revealing the structural and morphological distribution of material systems with three-dimensional (3D) network at micro-/nanoscale.This book chapter includes many examples on conventional and novel processes of FIB technologies, ranging from analysis of semiconductors to electron tomography-based imaging of hard materials such as nanoporous ceramics and composites. In addition, recent studies concerning the active use of dual-beam platforms are mentioned",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Meltem Sezen",authors:[{id:"176338",title:"Associate Prof.",name:"Meltem",middleName:null,surname:"Sezen",slug:"meltem-sezen",fullName:"Meltem Sezen"}]},{id:"50866",title:"Effects of Different Laser Pulse Regimes (Nanosecond, Picosecond and Femtosecond) on the Ablation of Materials for Production of Nanoparticles in Liquid Solution",slug:"effects-of-different-laser-pulse-regimes-nanosecond-picosecond-and-femtosecond-on-the-ablation-of-ma",totalDownloads:6073,totalCrossrefCites:10,totalDimensionsCites:34,abstract:"Ultra-short laser pulse interaction with materials has received much attention from researchers in micro- and nanomachining, especially for the generation of nanoparticles in liquid environments, because of the straightforward method and direct application for organic solvents. In addition, the colloidal nanoparticles produced by laser ablation have very high purity—they are free from surfactants and reaction products or by-products. In this chapter, nanosecond, picosecond and femtosecond laser pulse durations are compared in laser material processing. Due to the unique properties of the short and ultra-short laser pulse durations in material processing, they are more apparent in the production of precision material processing and generation of nanoparticles in liquid environments.",book:{id:"5236",slug:"high-energy-and-short-pulse-lasers",title:"High Energy and Short Pulse Lasers",fullTitle:"High Energy and Short Pulse Lasers"},signatures:"Abubaker Hassan Hamad",authors:[{id:"183494",title:"Dr.",name:"Abubaker",middleName:"Hassan",surname:"Hamad",slug:"abubaker-hamad",fullName:"Abubaker Hamad"}]},{id:"49537",title:"Electron Diffraction",slug:"electron-diffraction",totalDownloads:10111,totalCrossrefCites:10,totalDimensionsCites:31,abstract:"Electron microscopes are usually supplied with equipment for obtaining diffraction patterns and micrographs from the same area of a specimen and the best results are attained if the complete use is to be made of these combined facilities. Electron diffraction patterns are used to obtain quantitative data including phase identification, orientation relationship and crystal defects in materials, etc. At first, a general introduction including a geometrical and quantitative approach to electron diffraction from a crystalline specimen, the reciprocal lattice and electron diffraction in the electron microscope are presented. The scattering process by an individual atom as well as a crystal, the Bragg law, Laue conditions and structure factor are also discussed. Types of diffraction patterns such as ring pattern, spot pattern and Kikuchi pattern, and general and unique indexing diffraction patterns are explained. The procedure for indexing simple, complicated and imperfect patterns as well as Kikuchi lines and a combination of Kikuchi lines and spots is outlined. The known and unknown materials are identified by indexing patterns. Practical comparisons between various methods of analysing diffraction patterns are also described. The basic diffraction patterns and the fine structure in the patterns including specimen tilting experiments, orientation relationship determination, phase identification, twinning, second phases, crystallographic information, dislocation, preferred orientation and texture, extra spots and streaks are described in detail. Finally, electron diffraction patterns of new materials are investigated.",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Mohsen Asadi Asadabad and Mohammad Jafari Eskandari",authors:[{id:"176352",title:"Dr.",name:"Mohsen",middleName:null,surname:"Asadi Asadabad",slug:"mohsen-asadi-asadabad",fullName:"Mohsen Asadi Asadabad"},{id:"177600",title:"Dr.",name:"Mohammad",middleName:null,surname:"Jafari Eskandari",slug:"mohammad-jafari-eskandari",fullName:"Mohammad Jafari Eskandari"}]}],onlineFirstChaptersFilter:{topicId:"20",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82228",title:"Nonlinear Intelligent Predictive Control for the Yaw System of Large-Scale Wind Turbines",slug:"nonlinear-intelligent-predictive-control-for-the-yaw-system-of-large-scale-wind-turbines",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105484",abstract:"This chapter presents a nonlinear intelligent predictive control using multi-step prediction model for the electrical motor-based yaw system of an industrial wind turbine. The proposed method introduces a finite control set under constraints for the demanded yaw rate, predicts the multi-step yaw error using the control set element and the prediction wind directions, and employs an exhaustive search method to search the control output candidate giving the minimal value of the objective function. As the objective function is designed for a joint power and actuator usage optimization, the weighting factor in the objective function is optimally determined by the fuzzy regulator that is optimized by an intelligent algorithm. Finally, the proposed method is demonstrated by simulation tests using real wind direction data.",book:{id:"11499",title:"Nonlinear Systems - Recent Developments and Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11499.jpg"},signatures:"Dongran Song, Ziqun Li, Jian Yang, Mi Dong, Xiaojiao Chen and Liansheng Huang"},{id:"82102",title:"Vortex Analysis and Fluid Transport in Time-Dependent Flows",slug:"vortex-analysis-and-fluid-transport-in-time-dependent-flows",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.105196",abstract:"In this contribution, we present a set of procedures developed to identify fluid flow structures and characterize their space-time evolution in time-dependent flows. In particular, we consider two different contests of importance in applied fluid mechanics: 1) large-scale almost 2D atmospheric and oceanic flows and 2) flow inside the left ventricle in the human blood circulation. For both cases, we designed an ad hoc experimental model to reproduce and deeply investigate the considered phenomena. We will focus on the post-processing of high-resolution velocity data sets obtained via laboratory experiments by measuring the flow field using a technique based on image analysis. We show how the proposed methodologies represent a valid tool suitable for extracting the main patterns and quantify fluid transport in complex flows from both Eulerian and Lagrangian perspectives.",book:{id:"10958",title:"Vortex Dynamics - From Physical to Mathematical Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/10958.jpg"},signatures:"Stefania Espa, Maria Grazia Badas and Simon Cabanes"},{id:"82222",title:"High-Lying Confined Subbands in Terahertz Quantum Cascade Lasers",slug:"high-lying-confined-subbands-in-terahertz-quantum-cascade-lasers",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105479",abstract:"In designing the terahertz quantum cascade lasers, electron injection manner indeed plays a significant role to achieve the population inversion. The resonant tunneling process is commonly employed for this injection process but waste more than 50% fraction of populations out of the active region owing to resonance alignment, and the injection efficiency is obviously degraded due to thermal incoherence. An alternative approach is to consider the phonon-assisted injection process that basically contributes to most of the populations to the upper lasing level. However, this manner is still not realized in experiments if a short-period design only containing two quantum wells is used. In this work, it is found in this design that the population inversion is indeed well improved; however, the optical gain is inherently low even at a low temperature. Those two opposite trends are ascribed to a strong parasitic absorption overlapping the gain. The magnitude of this overlap is closely related to the lasing frequency, where frequencies below 3 THz suffer from fewer effects.",book:{id:"11495",title:"Fundamentals and Application of Femtosecond Optics",coverURL:"https://cdn.intechopen.com/books/images_new/11495.jpg"},signatures:"Li Wang"},{id:"81917",title:"Fluidics for Reconfigurable Microwave Components",slug:"fluidics-for-reconfigurable-microwave-components",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104857",abstract:"Dielectric and conducting liquids with varying electromagnetic properties can offer novel alternatives for building tunable microwave passive components as well as antennas. Injecting these fluidics in or around microwave substrates alters their overall electrical characteristics, enabling circuit reconfigurability. Alternatively, changing the shapes and dimensions of conductors by using liquid metals can achieve similar reconfigurability. An overview of different liquids and their electromagnetic properties is first given. The principles behind the reconfigurability of the electrical characteristics of typical guiding structures based on mode shape variation in the presence of fluids are discussed. The realization of an N-bit programmable impedance tuner in 3D LTCC technology based on these principles is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Dorra Bahloul, Ines Amor and Ammar Kouki"},{id:"82149",title:"Colorimetric Evaluations and Characterization of Natural and Synthetic Dyes/Pigments and Dyed Textiles and Related Products",slug:"colorimetric-evaluations-and-characterization-of-natural-and-synthetic-dyes-pigments-and-dyed-textil",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.104774",abstract:"This book chapter covers principles and few case studies on colorimetric Estimation of (i) determining purity/active ingredient % of selective dyes/pigments (ii) Identification of any colorants to distinguish from other similar compound, (iii) Measurement of surface colour strength of a dyed textile, (iv) Measurement of colour differences by estimating DE, DL*, Da*, Db*, DC and DH values, (v)Computer-aided colour match prediction for any standard shades, (vi) Estimation of compatibility of two dyes/colourants to use for compound shades, (vii) Determination of rate of dyeing, dyeing isotherm and dyeing kinetics to control dyeing, (viii) Optimization of dyeing process variables, (ix) Precession grading of Colour Fastness of dyed textiles on fading under different ways/agencies and (x) Estimation of Soil Removal efficacy of different detergent used for textiles. These colorimetric measurements are found to be very useful for effective process and product control of dyed textile materials. Selected Case studies on all the above colorimetric applications with specific example or experimented data are discussed for each of the method under reference. Finally, the other applications of colorimetric analysis besides textiles industry are also mentioned in concluding remarks.",book:{id:"11002",title:"Colorimetry",coverURL:"https://cdn.intechopen.com/books/images_new/11002.jpg"},signatures:"Ashis Kumar Samanta"},{id:"82116",title:"Thermo-Rheological Effect on Weak Nonlinear Rayleigh-Benard Convection under Rotation Speed Modulation",slug:"thermo-rheological-effect-on-weak-nonlinear-rayleigh-benard-convection-under-rotation-speed-modulati",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.105097",abstract:"The effects of rotation speed modulation and temperature-dependent viscosity on Rayleigh-Benard convection were investigated using a non-autonomous Ginzburg-Landau equation. The rotating temperature-dependent viscous fluid layer has been considered. The momentum equation with the Coriolis term has been used to describe finite-amplitude convective flow. The system is considered to be rotating about its vertical axis with a non-uniform rotation speed. In particular, we assume that the rotation speed is varying sinusoidally with time. Nusselt number is obtained in terms of the system parameters and graphically evaluated their effects. The effect of the modulated system diminishes the heat transfer more than the un-modulated system. Further, thermo-rheological parameter VT is found to destabilize the system.",book:{id:"11498",title:"Boundary Layer Flows - Modelling, Computation, and Applications of Laminar, Turbulent Incompressible and Compressible Flows",coverURL:"https://cdn.intechopen.com/books/images_new/11498.jpg"},signatures:"S.H. Manjula and Palle Kiran"}],onlineFirstChaptersTotal:50},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tSustainable development focuses on linking economic development with environmental protection and social development to ensure future prosperity for people and the planet. To tackle global challenges of development and environment, the United Nations General Assembly in 2015 adopted the 17 Sustainable Development Goals. SDGs emphasize that environmental sustainability should be strongly linked to socio-economic development, which should be decoupled from escalating resource use and environmental degradation for the purpose of reducing environmental stress, enhancing human welfare, and improving regional equity. Moreover, sustainable development seeks a balance between human development and decrease in ecological/environmental marginal benefits. Under the increasing stress of climate change, many environmental problems have emerged causing severe impacts at both global and local scales, driving ecosystem service reduction and biodiversity loss. Humanity’s relationship with resource exploitation and environment protection is a major global concern, as new threats to human and environmental security emerge in the Anthropocene. Currently, the world is facing significant challenges in environmental sustainability to protect global environments and to restore degraded ecosystems, while maintaining human development with regional equality. Thus, environmental sustainability with healthy natural ecosystems is critical to maintaining human prosperity in our warming planet.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11978,editor:{id:"61855",title:"Dr.",name:"Yixin",middleName:null,surname:"Zhang",slug:"yixin-zhang",fullName:"Yixin Zhang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYWJgQAO/Profile_Picture_2022-06-09T11:36:35.jpg",biography:"Professor Yixin Zhang is an aquatic ecologist with over 30 years of research and teaching experience in three continents (Asia, Europe, and North America) in Stream Ecology, Riparian Ecology, Urban Ecology, and Ecosystem Restoration and Aquatic Conservation, Human-Nature Interactions and Sustainability, Urbanization Impact on Aquatic Ecosystems. He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. 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